1 00:00:00,250 --> 00:00:01,800 The following content is provided 2 00:00:01,800 --> 00:00:04,040 under a Creative Commons license. 3 00:00:04,040 --> 00:00:06,890 Your support will help MIT OpenCourseWare continue 4 00:00:06,890 --> 00:00:10,740 to offer high quality educational resources for free. 5 00:00:10,740 --> 00:00:13,360 To make a donation or view additional materials 6 00:00:13,360 --> 00:00:17,241 from hundreds of MIT courses, visit MIT OpenCourseWare 7 00:00:17,241 --> 00:00:17,866 at ocw.mit.edu. 8 00:00:22,810 --> 00:00:29,650 PROFESSOR: I wanted to say a few things about the end of, 9 00:00:29,650 --> 00:00:32,180 what was meant to be the end of class six. 10 00:00:34,910 --> 00:00:36,880 It was chapter seven in the book. 11 00:00:43,940 --> 00:00:46,760 It was meant to be an overview of the forebrain. 12 00:00:46,760 --> 00:00:51,820 And at the end here I was talking 13 00:00:51,820 --> 00:00:56,950 about the-- we got through the limbic system, 14 00:00:56,950 --> 00:01:00,420 and then I wanted to say a little bit about the neocortex. 15 00:01:00,420 --> 00:01:07,385 So this picture here, this gives a little outline 16 00:01:07,385 --> 00:01:09,475 meant to show the addition of neocortex. 17 00:01:12,020 --> 00:01:14,610 Here is a slide where I'm showing 18 00:01:14,610 --> 00:01:17,760 that the limbic system is, one way to define 19 00:01:17,760 --> 00:01:20,040 it is by connections to the hypothalamus. 20 00:01:20,040 --> 00:01:23,790 But now when we get to the neocortex, 21 00:01:23,790 --> 00:01:27,890 the first topic that we always think of neocortex 22 00:01:27,890 --> 00:01:29,440 is as so important in learning. 23 00:01:29,440 --> 00:01:33,780 And I want to point out that it was in the early olfactory 24 00:01:33,780 --> 00:01:37,900 system, long before there was any neocortex, 25 00:01:37,900 --> 00:01:43,260 there evolved these two types of learning, 26 00:01:43,260 --> 00:01:47,380 that have remained the two major types of learning, that 27 00:01:47,380 --> 00:01:56,030 do involve neocortex in mammals, including the human beings. 28 00:01:56,030 --> 00:01:57,829 Two different kinds of learning. 29 00:01:57,829 --> 00:01:59,370 So what are these two different kinds 30 00:01:59,370 --> 00:02:02,420 of learning I'm talking about? 31 00:02:02,420 --> 00:02:04,910 You can think of them in terms of the structures that 32 00:02:04,910 --> 00:02:07,610 are involved, or you can give a name. 33 00:02:07,610 --> 00:02:10,121 The types of learning. 34 00:02:10,121 --> 00:02:13,440 You know what I'm talking about, any of you? 35 00:02:16,120 --> 00:02:19,630 Remember I talked about the early evolution of olfaction, 36 00:02:19,630 --> 00:02:23,710 and how the connections were with this ventral-most part 37 00:02:23,710 --> 00:02:26,060 of the striatum, the corpus striatum. 38 00:02:26,060 --> 00:02:29,055 And I said that the important thing about those connections 39 00:02:29,055 --> 00:02:32,220 was that they were plastic, they could change. 40 00:02:32,220 --> 00:02:41,145 That's how animals learn to like certain smells 41 00:02:41,145 --> 00:02:42,310 and not like others. 42 00:02:42,310 --> 00:02:46,880 They identify objects that way. 43 00:02:46,880 --> 00:02:49,440 But they did another thing, too. 44 00:02:49,440 --> 00:02:53,602 Different regions they went to smelled different. 45 00:02:53,602 --> 00:02:56,550 So without any vision, there were two kinds 46 00:02:56,550 --> 00:02:59,000 of learning that were possible. 47 00:02:59,000 --> 00:03:02,980 Places that were good or bad for them, according to the feedback 48 00:03:02,980 --> 00:03:04,500 they get, and the objects in those 49 00:03:04,500 --> 00:03:08,800 places that could be good or bad to eat, for example. 50 00:03:08,800 --> 00:03:10,780 They also, of course, could smell predators. 51 00:03:10,780 --> 00:03:12,490 And that's still true in many mammals. 52 00:03:16,650 --> 00:03:18,860 So this is the way I summarized it. 53 00:03:18,860 --> 00:03:24,770 Learned object preferences with identification of objects 54 00:03:24,770 --> 00:03:27,150 according to whether they're good or bad. 55 00:03:27,150 --> 00:03:29,410 And place learning, identification memory 56 00:03:29,410 --> 00:03:32,760 of good places and bad places. 57 00:03:32,760 --> 00:03:36,120 The first one is striatal dependent. 58 00:03:36,120 --> 00:03:39,280 And that remains true even though the habits 59 00:03:39,280 --> 00:03:44,800 formed aren't dependent so much on olfaction. 60 00:03:44,800 --> 00:03:49,650 In primates they're mostly dependent on other senses, 61 00:03:49,650 --> 00:03:52,020 but olfaction is still important. 62 00:03:52,020 --> 00:03:53,470 The other is place learning. 63 00:03:53,470 --> 00:03:56,660 And that has become critical for what humans usually 64 00:03:56,660 --> 00:03:59,815 think of when they think of memory, long-term memory 65 00:03:59,815 --> 00:04:00,315 formation. 66 00:04:03,630 --> 00:04:08,670 And that will be a theme that will recur in the class. 67 00:04:11,490 --> 00:04:16,120 And what is the part of the brain involved here? 68 00:04:16,120 --> 00:04:18,540 We always think of hippocampus. 69 00:04:18,540 --> 00:04:22,450 But in many animals, long before you could really 70 00:04:22,450 --> 00:04:24,615 identify something that looked like a seahorse 71 00:04:24,615 --> 00:04:27,700 or a hippocampus, it was part of the pallium. 72 00:04:27,700 --> 00:04:31,260 It was the medial pallium. 73 00:04:31,260 --> 00:04:35,490 In a picture like this, it's this part here. 74 00:04:35,490 --> 00:04:37,056 It's meant to be medial. 75 00:04:37,056 --> 00:04:38,930 It's a little hard to show medial and lateral 76 00:04:38,930 --> 00:04:40,140 in a picture like this. 77 00:04:40,140 --> 00:04:44,162 But it's part of the limbic system, connected 78 00:04:44,162 --> 00:04:44,995 to the hypothalamus. 79 00:04:44,995 --> 00:04:50,050 And we're going to discuss later why that came to be true. 80 00:04:50,050 --> 00:04:51,650 How that evolved. 81 00:04:51,650 --> 00:04:56,100 There are good reasons why we became so dependent on parts 82 00:04:56,100 --> 00:04:58,170 of the limbic system for our memories. 83 00:05:05,590 --> 00:05:09,660 So now, with neocortex expansion there 84 00:05:09,660 --> 00:05:13,220 were new sensory pathways that became prominent. 85 00:05:13,220 --> 00:05:15,380 They were more rapidly conducting 86 00:05:15,380 --> 00:05:17,450 than the spinal reticular pathways 87 00:05:17,450 --> 00:05:21,680 and the spinal thalamic pathways in sending information 88 00:05:21,680 --> 00:05:24,880 to the forebrain. 89 00:05:24,880 --> 00:05:27,280 Now we're talking mainly about pathways to neocortex. 90 00:05:29,810 --> 00:05:34,450 And here I'm just showing the addition of cortex. 91 00:05:34,450 --> 00:05:38,040 And then here I've altered this diagram 92 00:05:38,040 --> 00:05:41,840 here to show neocortex up here. 93 00:05:41,840 --> 00:05:43,909 There's the medial pallium. 94 00:05:43,909 --> 00:05:45,450 So I made it look like a hippocampus. 95 00:05:48,200 --> 00:05:49,950 So that's part of the limbic system, which 96 00:05:49,950 --> 00:05:55,050 is all of this in the diagram. 97 00:05:55,050 --> 00:05:59,790 And this is really also limbic, but it's olfactory. 98 00:05:59,790 --> 00:06:02,380 The olfactory parts of the limbic system. 99 00:06:02,380 --> 00:06:04,380 They're limbic because they're closely connected 100 00:06:04,380 --> 00:06:06,200 with hypothalamus. 101 00:06:06,200 --> 00:06:08,637 In fact, many animals actually have direct olfactory 102 00:06:08,637 --> 00:06:09,970 connections to the hypothalamus. 103 00:06:13,010 --> 00:06:15,480 So now the two pathways. 104 00:06:15,480 --> 00:06:17,070 I don't know why, but students always 105 00:06:17,070 --> 00:06:21,040 find it difficult to memorize this. 106 00:06:21,040 --> 00:06:23,590 We talked about spinal reticular, 107 00:06:23,590 --> 00:06:25,815 we talked about spinal thalamic. 108 00:06:25,815 --> 00:06:30,610 Now here is another system that has a number of branches, 109 00:06:30,610 --> 00:06:35,750 but many more of its axons go all the way to the thalamus. 110 00:06:35,750 --> 00:06:37,900 So it's a pathway to the neocortex 111 00:06:37,900 --> 00:06:39,750 by way of the thalamus. 112 00:06:39,750 --> 00:06:43,280 And I've shown here that the first part of it 113 00:06:43,280 --> 00:06:45,790 is the dorsal columns. 114 00:06:45,790 --> 00:06:49,660 They are actually axons of primary sensory neurons. 115 00:06:49,660 --> 00:06:51,620 So here they start, out on the skin. 116 00:06:51,620 --> 00:06:57,390 Specialized end organs like Pacinian corpuscles, 117 00:06:57,390 --> 00:07:02,220 sensitive to touch and things like that, in the skin. 118 00:07:02,220 --> 00:07:03,570 There's its axon. 119 00:07:03,570 --> 00:07:04,390 It does branch. 120 00:07:04,390 --> 00:07:06,450 It connects in the spinal cord, too. 121 00:07:06,450 --> 00:07:09,380 But it ascends all the way to the top of the spinal cord. 122 00:07:09,380 --> 00:07:12,900 And some anatomy texts say caudal end of the hindbrain. 123 00:07:12,900 --> 00:07:15,890 It's a little bit arbitrary where you mark that division. 124 00:07:15,890 --> 00:07:17,300 I follow [INAUDIBLE]. 125 00:07:17,300 --> 00:07:19,230 He puts it at the very top of the spinal cord. 126 00:07:19,230 --> 00:07:21,450 That's the dorsal column nuclei. 127 00:07:26,270 --> 00:07:28,640 We'll be talking about that very soon. 128 00:07:28,640 --> 00:07:33,760 We'll see the dorsal column nuclei, 129 00:07:33,760 --> 00:07:37,890 representing all different parts of the body except the face. 130 00:07:37,890 --> 00:07:40,535 But in fact, the face is represented there too, 131 00:07:40,535 --> 00:07:42,770 and I will show you how. 132 00:07:42,770 --> 00:07:46,860 But that is the first synapse in the pathway. 133 00:07:46,860 --> 00:07:49,010 So it conducts rapidly. 134 00:07:49,010 --> 00:07:53,530 They tend to be all myelinated, fairly large axons. 135 00:07:53,530 --> 00:07:57,960 So this pathway now, from the dorsal column nuclei, 136 00:07:57,960 --> 00:08:03,640 decussates right here and ascends in a pathway 137 00:08:03,640 --> 00:08:06,250 through the hindbrain and midbrain that we call 138 00:08:06,250 --> 00:08:09,920 the medial lemniscus, the medial ribbon. 139 00:08:09,920 --> 00:08:14,200 So that goes directly to the thalamus. 140 00:08:14,200 --> 00:08:20,940 There are a few branches that go into reticular formation, 141 00:08:20,940 --> 00:08:23,830 but the main pathway goes right to the thalamus. 142 00:08:23,830 --> 00:08:28,000 And those thalamic cells connect to somatosensory neocortex. 143 00:08:28,000 --> 00:08:33,700 That's how our somatosensory cortex gets its major input. 144 00:08:33,700 --> 00:08:36,549 It does get input through the spinal thalamic pathway, 145 00:08:36,549 --> 00:08:40,419 and even a little bit from the spinal reticular also. 146 00:08:40,419 --> 00:08:44,430 But at least for fine touch, very discriminative 147 00:08:44,430 --> 00:08:47,610 touch, especially the touch that we 148 00:08:47,610 --> 00:08:51,070 use when we're moving our fingers over something, very 149 00:08:51,070 --> 00:08:53,640 dependent on this pathway. 150 00:08:53,640 --> 00:08:55,370 So here is the top view. 151 00:08:55,370 --> 00:08:57,380 It shows the same thing. 152 00:08:57,380 --> 00:09:01,370 The primary sensory neuron and its axon terminating. 153 00:09:01,370 --> 00:09:04,670 If this is in the lumbar enlargement, 154 00:09:04,670 --> 00:09:06,790 so lets say it's coming from the foot, 155 00:09:06,790 --> 00:09:12,410 it would go to the medial dorsal column nucleus. 156 00:09:12,410 --> 00:09:14,220 There's two nuclei there. 157 00:09:14,220 --> 00:09:17,160 The medial one represents the lower body, 158 00:09:17,160 --> 00:09:21,380 and the upper one represents the arms and chest. 159 00:09:21,380 --> 00:09:23,700 And there's the axon that decussates. 160 00:09:23,700 --> 00:09:26,785 The axon of the medial lemniscus starts from the dorsal column 161 00:09:26,785 --> 00:09:31,130 nuclei, crosses over, goes to the thalamus. 162 00:09:31,130 --> 00:09:33,490 So it's a crossed pathway. 163 00:09:33,490 --> 00:09:39,270 So that all evolved after the crossing evolved. 164 00:09:39,270 --> 00:09:43,700 Which was admittedly very early, very early chordates. 165 00:09:47,230 --> 00:09:49,230 But if we look at the most ancient ones, 166 00:09:49,230 --> 00:09:51,810 we look at hagfish, we look at sea lamprey, 167 00:09:51,810 --> 00:09:54,590 they don't have any pathway resembling this. 168 00:09:54,590 --> 00:09:56,850 In fact, most mammals don't have much 169 00:09:56,850 --> 00:09:59,320 of a pathway that's like this one. 170 00:09:59,320 --> 00:10:03,010 It's the mammals this becomes prominent, 171 00:10:03,010 --> 00:10:06,160 and other advanced vertebrates like birds. 172 00:10:08,930 --> 00:10:13,030 And now, along with that, you get descending pathways 173 00:10:13,030 --> 00:10:16,280 coming down from those somatosensory regions. 174 00:10:16,280 --> 00:10:19,450 And one of the somatosensory regions 175 00:10:19,450 --> 00:10:22,240 became more specialized for controlling fine movement. 176 00:10:22,240 --> 00:10:25,200 That was the motor cortex. 177 00:10:25,200 --> 00:10:28,430 So I'm showing it here on the side view. 178 00:10:28,430 --> 00:10:31,630 And I'm depicting two neurons for a good reason. 179 00:10:31,630 --> 00:10:35,400 Because I want to point out that the somatosensory, what we 180 00:10:35,400 --> 00:10:39,770 call somatosensory cortex, and motor cortex, 181 00:10:39,770 --> 00:10:43,327 both have pathways to the spinal cord. 182 00:10:43,327 --> 00:10:45,410 Here's the one you're probably most familiar with. 183 00:10:45,410 --> 00:10:48,730 It comes from motor cortex. 184 00:10:48,730 --> 00:10:53,790 Note that there are branches to the striatum, to the thalamus, 185 00:10:53,790 --> 00:10:57,020 to the midbrain, to the hindbrain, 186 00:10:57,020 --> 00:10:59,050 especially to the pons. 187 00:10:59,050 --> 00:11:01,205 But it goes all the way down to the spinal cord, 188 00:11:01,205 --> 00:11:03,720 where most of the axons and interneurons 189 00:11:03,720 --> 00:11:06,350 are in the ventral horn. 190 00:11:06,350 --> 00:11:08,640 A few of them, as I showed here, go directly 191 00:11:08,640 --> 00:11:09,820 to the motor neurons. 192 00:11:09,820 --> 00:11:13,550 Now the somatosensory cortex has similarly 193 00:11:13,550 --> 00:11:16,640 descending pathways all the way to the spinal cord. 194 00:11:16,640 --> 00:11:20,520 But these terminate in the dorsal horn, 195 00:11:20,520 --> 00:11:23,110 the part of the spinal cord that gets the sensory input 196 00:11:23,110 --> 00:11:24,266 from the dorsal roots. 197 00:11:24,266 --> 00:11:27,450 We'll show the adult. 198 00:11:27,450 --> 00:11:32,700 We'll be talking a little more about that very soon. 199 00:11:32,700 --> 00:11:34,860 Here shows that that, of course, has 200 00:11:34,860 --> 00:11:37,560 to be a decussating pathway, too. 201 00:11:37,560 --> 00:11:41,945 Because we know that the opposite side of the body is 202 00:11:41,945 --> 00:11:42,445 represented. 203 00:11:45,570 --> 00:11:47,800 If this is the left side, it's represented 204 00:11:47,800 --> 00:11:49,690 on the right side of the brain. 205 00:11:49,690 --> 00:11:53,230 So that pathway way decussates too at about the same place 206 00:11:53,230 --> 00:11:55,590 the medial lemniscus decussates. 207 00:11:55,590 --> 00:12:00,450 At the caudal, that's a very dramatic place in the brain, 208 00:12:00,450 --> 00:12:02,970 between hindbrain and spinal cord, 209 00:12:02,970 --> 00:12:04,840 because of the major decussations that 210 00:12:04,840 --> 00:12:08,660 occur there just above the dorsal column nuclei. 211 00:12:11,690 --> 00:12:16,000 I mentioned birds have this too. 212 00:12:16,000 --> 00:12:21,030 You have a structure in birds, particularly prominent 213 00:12:21,030 --> 00:12:28,200 in the more advanced birds like owls and other raptors, 214 00:12:28,200 --> 00:12:30,250 but many birds have this. 215 00:12:30,250 --> 00:12:34,280 The word wulst in German means a bulge. 216 00:12:34,280 --> 00:12:38,660 And it does form a bulge in the hemispheres of these animals. 217 00:12:38,660 --> 00:12:42,750 And they have a motor wulst just like our motor cortex. 218 00:12:42,750 --> 00:12:45,860 It projects directly to the spinal cord. 219 00:12:45,860 --> 00:12:48,730 They do have somatosensory wulsts and visual wulsts 220 00:12:48,730 --> 00:12:50,730 as well. 221 00:12:50,730 --> 00:12:53,090 They also have a very large subcortical region 222 00:12:53,090 --> 00:12:55,600 that has connections also like neocortex, 223 00:12:55,600 --> 00:12:59,857 just like the wulst does, but it doesn't require cortex at all. 224 00:12:59,857 --> 00:13:00,940 It's actually subcortical. 225 00:13:04,110 --> 00:13:08,130 It's called the nested pallium, or the nidopallium. 226 00:13:08,130 --> 00:13:11,962 We'll mention that a few times. 227 00:13:11,962 --> 00:13:18,140 Just so you know something about other companions, 228 00:13:18,140 --> 00:13:19,160 advanced vertebrates. 229 00:13:22,920 --> 00:13:26,010 Now let's just mention very briefly 230 00:13:26,010 --> 00:13:28,100 what characterizes the sensory and motor 231 00:13:28,100 --> 00:13:31,980 functions of the neocortex and what other types of functions 232 00:13:31,980 --> 00:13:34,090 depend on neocortex. 233 00:13:34,090 --> 00:13:39,510 Think of neocortex as adding to sensory processes. 234 00:13:39,510 --> 00:13:46,680 Acuity, both sensory and motor, fine movement control, 235 00:13:46,680 --> 00:13:49,650 find discrimination of objects. 236 00:13:49,650 --> 00:13:53,430 But it also made it better at objects 237 00:13:53,430 --> 00:13:56,460 could be separated from the background more easily. 238 00:13:56,460 --> 00:14:00,630 So it's not just a mishmash of stimuli they're responding to, 239 00:14:00,630 --> 00:14:02,630 but they respond to specific objects. 240 00:14:02,630 --> 00:14:05,070 So that means they have to form images of those objects. 241 00:14:05,070 --> 00:14:06,830 And that's something neocortex does. 242 00:14:09,700 --> 00:14:13,260 And I think the most unique thing about neocortex-- 243 00:14:13,260 --> 00:14:17,590 just that fine control, the acuity, sensory-motor, 244 00:14:17,590 --> 00:14:21,790 that's just sort of a quantitative improvement 245 00:14:21,790 --> 00:14:24,630 over what lower structures did. 246 00:14:24,630 --> 00:14:28,100 But this is something really unique. 247 00:14:28,100 --> 00:14:32,640 It adds the ability to anticipate and plan. 248 00:14:32,640 --> 00:14:37,350 Anticipate stimuli, we do that with image formation. 249 00:14:37,350 --> 00:14:41,140 Imaging depends on the posture of parts of the neocortex. 250 00:14:41,140 --> 00:14:42,840 And also we plan movements. 251 00:14:42,840 --> 00:14:46,240 We don't just react. 252 00:14:46,240 --> 00:14:48,680 That uses an internal model, a kind 253 00:14:48,680 --> 00:14:49,990 of simulation of the world. 254 00:14:49,990 --> 00:14:52,780 It depends on those images as well. 255 00:14:52,780 --> 00:14:56,870 So those are really the unique parts. 256 00:14:56,870 --> 00:14:59,150 I put review slides at the end of this chapter 257 00:14:59,150 --> 00:15:00,360 that you should look at. 258 00:15:03,030 --> 00:15:08,880 I want to get on here with the main topic 259 00:15:08,880 --> 00:15:12,040 of the day, formation of the neural tube 260 00:15:12,040 --> 00:15:15,690 in the embryo-- how central nervous system 261 00:15:15,690 --> 00:15:17,630 development begins. 262 00:15:17,630 --> 00:15:20,100 And we'll focus on the spinal level. 263 00:15:20,100 --> 00:15:23,600 That is where the neural tube first fully forms. 264 00:15:23,600 --> 00:15:26,800 But the entire central nervous system begins as a tube. 265 00:15:31,360 --> 00:15:33,240 Remember, it all evolves, actually, together. 266 00:15:37,460 --> 00:15:39,460 So we're going to do the embryology today. 267 00:15:39,460 --> 00:15:42,529 And next time we'll be able to get to the adult spinal cord, 268 00:15:42,529 --> 00:15:44,320 and then also the autonomic nervous system. 269 00:15:46,920 --> 00:15:49,830 These are the stages of development 270 00:15:49,830 --> 00:15:51,600 of a nervous system. 271 00:15:51,600 --> 00:15:56,730 After the egg is fertilized you get the formation 272 00:15:56,730 --> 00:15:58,720 of a morula, a clump of cells. 273 00:15:58,720 --> 00:16:02,800 That becomes a blastula, which is a hollow ball of cells. 274 00:16:02,800 --> 00:16:04,870 Now it's got fluid in the middle. 275 00:16:04,870 --> 00:16:09,160 Then a major step, gastrulation, where 276 00:16:09,160 --> 00:16:15,255 the organism, instead of just this hollow ball of cells 277 00:16:15,255 --> 00:16:18,945 with fluid in the middle, becomes shaped like a doughnut. 278 00:16:18,945 --> 00:16:23,110 The formation of the alimentary canal-- mouth at one end, 279 00:16:23,110 --> 00:16:24,220 anus at the other. 280 00:16:24,220 --> 00:16:25,520 That forms very early. 281 00:16:25,520 --> 00:16:26,710 We'll see pictures of that. 282 00:16:26,710 --> 00:16:29,130 And then finally neurulation, the formation 283 00:16:29,130 --> 00:16:33,970 of the nervous system, the major thing we want to talk about. 284 00:16:33,970 --> 00:16:36,950 Now, Lewis Wolpert, in his very interesting little book, 285 00:16:36,950 --> 00:16:39,700 Triumph of the Embryo, when he revised it, 286 00:16:39,700 --> 00:16:42,460 other authors joined him and it became 287 00:16:42,460 --> 00:16:45,830 a more standard embryology book. 288 00:16:45,830 --> 00:16:47,730 This is also very interesting. 289 00:16:47,730 --> 00:16:50,230 All of the things that I found in Triumph of the Embryo 290 00:16:50,230 --> 00:16:53,450 are still there, but he really simplified it 291 00:16:53,450 --> 00:16:56,380 and talked about the major principles. 292 00:16:56,380 --> 00:16:57,960 And one of the things he laid out 293 00:16:57,960 --> 00:17:03,090 was the cellular events, what are the cellular events that 294 00:17:03,090 --> 00:17:06,050 characterize development of the nervous system? 295 00:17:08,710 --> 00:17:09,329 What are they? 296 00:17:12,400 --> 00:17:14,000 Well, contraction. 297 00:17:14,000 --> 00:17:16,380 Parts of the cell could contract. 298 00:17:16,380 --> 00:17:18,020 What does that involve? 299 00:17:18,020 --> 00:17:20,260 In involves contractile proteins, 300 00:17:20,260 --> 00:17:22,869 just like we have in muscle. 301 00:17:22,869 --> 00:17:27,030 Cells have that also, to some degree, in development. 302 00:17:30,540 --> 00:17:32,440 Contraction. 303 00:17:32,440 --> 00:17:38,130 Well, cells have to, in order to form organized tissue, cells 304 00:17:38,130 --> 00:17:42,200 have to be able to stick to things, stick to each other 305 00:17:42,200 --> 00:17:46,150 to form these little processes that can adhere to something. 306 00:17:46,150 --> 00:17:47,580 So they show adhesion. 307 00:17:47,580 --> 00:17:51,680 And the adhesive properties through cell 308 00:17:51,680 --> 00:17:53,860 adhesion molecules in the membrane, which 309 00:17:53,860 --> 00:17:58,150 can change during the course of development. 310 00:17:58,150 --> 00:18:00,480 That's a big part of development, selective adhesion 311 00:18:00,480 --> 00:18:03,970 and changes in adhesion. 312 00:18:03,970 --> 00:18:06,010 And then cells can move. 313 00:18:06,010 --> 00:18:07,940 How do they move? 314 00:18:07,940 --> 00:18:10,710 So we'll be talking about that. 315 00:18:10,710 --> 00:18:13,730 And finally, of course, growth. 316 00:18:13,730 --> 00:18:16,300 And by growth, often an embryologist 317 00:18:16,300 --> 00:18:19,700 is talking about growth by proliferation 318 00:18:19,700 --> 00:18:22,750 of cells, mitosis. 319 00:18:22,750 --> 00:18:25,700 It also means growth and increased size of cells. 320 00:18:25,700 --> 00:18:28,616 But the main factor is increased numbers of cells. 321 00:18:33,860 --> 00:18:37,770 So here's the pictures that Wolpert uses. 322 00:18:37,770 --> 00:18:43,840 From a single fertilized egg here, to the morula. 323 00:18:43,840 --> 00:18:46,600 It looks like a raspberry. 324 00:18:46,600 --> 00:18:51,000 And here it becomes the blastula with fluid in the middle. 325 00:18:51,000 --> 00:18:55,030 And then note some cells have moved to the interior. 326 00:18:55,030 --> 00:19:00,680 And there's more contraction at one side, 327 00:19:00,680 --> 00:19:02,940 the outside of the cell, than on the inside. 328 00:19:02,940 --> 00:19:06,630 And that leads to invagination that you see beginning here. 329 00:19:06,630 --> 00:19:09,820 And then look what happens. 330 00:19:09,820 --> 00:19:12,650 These little processes extend out. 331 00:19:12,650 --> 00:19:15,160 Those little filaments are called 332 00:19:15,160 --> 00:19:19,720 filopodia, filamentous feet. 333 00:19:19,720 --> 00:19:21,830 They extend out, and they actually 334 00:19:21,830 --> 00:19:24,540 reach the other side, where they adhere. 335 00:19:24,540 --> 00:19:27,430 So now you have adhesion. 336 00:19:27,430 --> 00:19:29,340 You have both of these processes we just 337 00:19:29,340 --> 00:19:34,860 talked about are happening, contraction and adhesion. 338 00:19:34,860 --> 00:19:38,380 Movement-- notice the movement that's 339 00:19:38,380 --> 00:19:41,890 being caused by the contraction, contractile proteins 340 00:19:41,890 --> 00:19:43,816 in those filopodia. 341 00:19:43,816 --> 00:19:48,920 So it pulls this side of the embryo right across. 342 00:19:48,920 --> 00:19:51,210 And that causes changes that cause 343 00:19:51,210 --> 00:19:56,100 an opening to form between here and here. 344 00:19:56,100 --> 00:19:59,650 The cells continue to move to the inside. 345 00:19:59,650 --> 00:20:03,480 But that process from here to hear, or actually 346 00:20:03,480 --> 00:20:06,729 all along the bottom, is called gastrulation. 347 00:20:06,729 --> 00:20:08,145 This is just seen in the sections. 348 00:20:11,040 --> 00:20:13,620 This shows us one of the cells, how 349 00:20:13,620 --> 00:20:17,540 complicated they can be with their various extensions 350 00:20:17,540 --> 00:20:19,070 and movement. 351 00:20:19,070 --> 00:20:25,960 Because if this was all there was, we'd have one layer. 352 00:20:25,960 --> 00:20:27,890 That outer layer is the ectoderm. 353 00:20:27,890 --> 00:20:30,930 But cells move inward. 354 00:20:30,930 --> 00:20:32,210 They move to the interior. 355 00:20:32,210 --> 00:20:35,300 And that becomes the mesoderm and the endoderm. 356 00:20:35,300 --> 00:20:37,715 Mesoderm forming muscle and skeleton, 357 00:20:37,715 --> 00:20:40,516 and the endoderm forming the internal organs. 358 00:20:44,320 --> 00:20:52,070 So then none of this gives you a central nervous system. 359 00:20:52,070 --> 00:20:56,300 How do we get a central nervous system out of that? 360 00:20:56,300 --> 00:20:59,410 So we need to talk about neurulation, 361 00:20:59,410 --> 00:21:01,820 the formation of the neural tube. 362 00:21:01,820 --> 00:21:05,620 And then proliferation of the cells, migration of cells, 363 00:21:05,620 --> 00:21:07,160 and differentiation of cells. 364 00:21:07,160 --> 00:21:10,920 By differentiation we mean the cell 365 00:21:10,920 --> 00:21:14,170 changes so the cells look different from each other. 366 00:21:14,170 --> 00:21:15,700 They differentiate from each other. 367 00:21:15,700 --> 00:21:20,680 They form dendrites, they form axons, if they're neurons. 368 00:21:20,680 --> 00:21:23,014 If they're glial cells they also form processes, 369 00:21:23,014 --> 00:21:24,680 depending on what kind of glia they are. 370 00:21:27,940 --> 00:21:29,720 So these are the questions I'm asking. 371 00:21:29,720 --> 00:21:32,630 First of all, what is the notochord? 372 00:21:32,630 --> 00:21:35,140 We've heard that term used before. 373 00:21:35,140 --> 00:21:38,270 You should remember what it is. 374 00:21:38,270 --> 00:21:39,680 Some of you might. 375 00:21:39,680 --> 00:21:42,290 What is the notochord? 376 00:21:42,290 --> 00:21:45,010 It's not in all animals. 377 00:21:45,010 --> 00:21:49,390 It's just in all animals that we call chordates. 378 00:21:49,390 --> 00:21:50,822 So what is it? 379 00:21:50,822 --> 00:21:53,360 The notochord. 380 00:21:53,360 --> 00:21:55,790 Yes? 381 00:21:55,790 --> 00:22:00,790 AUDIENCE: The cartilaginous tube that becomes the 382 00:22:00,790 --> 00:22:01,750 PROFESSOR: Yes. 383 00:22:01,750 --> 00:22:04,110 Tube may not be the most accurate. 384 00:22:04,110 --> 00:22:06,770 It's cartilaginous for sure. 385 00:22:06,770 --> 00:22:08,200 What is it? 386 00:22:08,200 --> 00:22:09,825 AUDIENCE: It's beneath the neural tube. 387 00:22:13,100 --> 00:22:14,670 PROFESSOR: But wait. 388 00:22:14,670 --> 00:22:18,390 It precedes the neural tube. 389 00:22:18,390 --> 00:22:21,700 But where in the organism? 390 00:22:21,700 --> 00:22:25,974 At least, what does it become in the organism? 391 00:22:25,974 --> 00:22:28,147 AUDIENCE: In the back. 392 00:22:28,147 --> 00:22:28,980 PROFESSOR: The back. 393 00:22:28,980 --> 00:22:29,940 Exactly. 394 00:22:29,940 --> 00:22:32,760 It's always along the back. 395 00:22:32,760 --> 00:22:34,590 At least what's going to become the back. 396 00:22:34,590 --> 00:22:37,230 Maybe that's how it becomes a back. 397 00:22:37,230 --> 00:22:39,750 The notochord is at the surface, one side, 398 00:22:39,750 --> 00:22:41,986 that becomes the back. 399 00:22:41,986 --> 00:22:43,694 AUDIENCE: Does notochord become backbone? 400 00:22:47,630 --> 00:22:50,380 PROFESSOR: It doesn't become the backbone, 401 00:22:50,380 --> 00:22:55,350 but the skeletal elements form around it. 402 00:22:55,350 --> 00:22:57,320 There are induction processes. 403 00:22:57,320 --> 00:23:01,870 Molecules coming from the notochord exert really powerful 404 00:23:01,870 --> 00:23:03,200 changes. 405 00:23:03,200 --> 00:23:06,100 First of all in the formation of the nervous system, but then 406 00:23:06,100 --> 00:23:07,825 the formation of the skeleton as well. 407 00:23:12,520 --> 00:23:20,000 Who discovered this phenomenon of induction of the CNS? 408 00:23:20,000 --> 00:23:23,270 Now, we know now that the inductive process, 409 00:23:23,270 --> 00:23:25,460 the notochord induces the formation 410 00:23:25,460 --> 00:23:27,000 of the nervous system. 411 00:23:27,000 --> 00:23:29,430 But how was it discovered? 412 00:23:29,430 --> 00:23:32,840 Who discovered that there's some kind of induction that's 413 00:23:32,840 --> 00:23:34,250 happening? 414 00:23:34,250 --> 00:23:37,482 Because if you move things around, 415 00:23:37,482 --> 00:23:39,440 you can get nervous system forming differently, 416 00:23:39,440 --> 00:23:40,398 or in different places. 417 00:23:42,900 --> 00:23:44,630 Remember the names? 418 00:23:44,630 --> 00:23:46,850 There were actually two people, but only one of them 419 00:23:46,850 --> 00:23:49,220 got the Nobel Prize for it. 420 00:23:51,750 --> 00:23:55,170 His name was Hans Spemann. 421 00:23:55,170 --> 00:23:56,590 Spemann got the prize. 422 00:23:56,590 --> 00:23:58,870 But the discovery was made in his lab 423 00:23:58,870 --> 00:24:03,360 by his student, a young woman named Hilde Mangold. 424 00:24:07,700 --> 00:24:10,670 Why didn't she get the Nobel Prize? 425 00:24:10,670 --> 00:24:13,890 Unfortunately, they don't give Nobel Prizes to someone 426 00:24:13,890 --> 00:24:16,090 who has died. 427 00:24:16,090 --> 00:24:22,340 She died in a kitchen accident when she was only 26 years old. 428 00:24:22,340 --> 00:24:25,135 But she should be remembered just as Spemann 429 00:24:25,135 --> 00:24:27,230 is for the discovery of induction 430 00:24:27,230 --> 00:24:28,652 of the nervous system. 431 00:24:33,280 --> 00:24:36,650 And then we want to know what neural crest cells are. 432 00:24:36,650 --> 00:24:40,026 You've got to know something about the neural tube formation 433 00:24:40,026 --> 00:24:43,220 to be able to answer that. 434 00:24:43,220 --> 00:24:46,010 I should have a piece of paper here. 435 00:24:46,010 --> 00:24:48,130 I didn't bring my piece of paper. 436 00:24:48,130 --> 00:24:50,610 You just take a piece of paper and push at the two ends. 437 00:24:50,610 --> 00:24:52,350 What happens? 438 00:24:52,350 --> 00:24:53,980 It will indent, right? 439 00:24:53,980 --> 00:24:56,100 And you can get it to indent in one place. 440 00:24:56,100 --> 00:25:00,410 That's what happens to the nervous system here. 441 00:25:00,410 --> 00:25:01,440 Here's a sheet of paper. 442 00:25:01,440 --> 00:25:05,790 It's one cell thick ectoderm. 443 00:25:05,790 --> 00:25:09,200 And that is the notochord. 444 00:25:09,200 --> 00:25:11,869 This is just part of the ectoderm, the part that 445 00:25:11,869 --> 00:25:13,410 will become the back of the organism. 446 00:25:16,170 --> 00:25:18,030 There's the notochord. 447 00:25:18,030 --> 00:25:20,870 Then there's an influence from the notochord. 448 00:25:20,870 --> 00:25:25,460 Note here I show cells getting thicker in this region. 449 00:25:25,460 --> 00:25:29,360 That's what we call a neural plate. 450 00:25:29,360 --> 00:25:31,380 The cells are already determined now. 451 00:25:31,380 --> 00:25:33,880 Which ones are going to become nervous system 452 00:25:33,880 --> 00:25:38,100 and which will remain other parts of the ectoderm, 453 00:25:38,100 --> 00:25:38,860 like the skin. 454 00:25:42,870 --> 00:25:47,750 And then, because of differences in contraction, 455 00:25:47,750 --> 00:25:50,527 despite during gastrulation earlier, 456 00:25:50,527 --> 00:25:51,610 you get an endogenization. 457 00:25:54,820 --> 00:25:56,880 So it doesn't really happen because somebody 458 00:25:56,880 --> 00:26:00,310 pushed the sides like a piece of paper. 459 00:26:00,310 --> 00:26:02,660 But the dynamics are very similar. 460 00:26:02,660 --> 00:26:08,170 So it starts to form a groove along the back of the organism. 461 00:26:08,170 --> 00:26:10,500 So think of it in three dimensions. 462 00:26:10,500 --> 00:26:12,640 That's why I like you to think of a piece of paper. 463 00:26:12,640 --> 00:26:16,260 If we push in, it's gonna form a groove 464 00:26:16,260 --> 00:26:19,560 all along the back of the organism. 465 00:26:19,560 --> 00:26:21,260 There's the notochord. 466 00:26:21,260 --> 00:26:24,965 The molecules emanating from that notochord 467 00:26:24,965 --> 00:26:32,610 are what's causing these changes in the ectoderm above it. 468 00:26:32,610 --> 00:26:37,350 And note I show two little bulges on the sides. 469 00:26:37,350 --> 00:26:39,590 That is called the neural crest. 470 00:26:39,590 --> 00:26:41,100 And it's very different. 471 00:26:41,100 --> 00:26:44,010 Because as these two edges come together 472 00:26:44,010 --> 00:26:47,810 so you end up with a tube, these cells 473 00:26:47,810 --> 00:26:49,060 don't become part of the tube. 474 00:26:49,060 --> 00:26:50,900 They stay on the outside. 475 00:26:50,900 --> 00:26:52,960 It's those neural crest cells that 476 00:26:52,960 --> 00:26:56,050 form the peripheral nervous system. 477 00:26:56,050 --> 00:26:59,540 All the cells of the peripheral nervous system 478 00:26:59,540 --> 00:27:03,960 come from the neural crest at this level 479 00:27:03,960 --> 00:27:05,930 of the nervous system. 480 00:27:05,930 --> 00:27:07,620 Now, there are cells that don't come 481 00:27:07,620 --> 00:27:10,190 from neural crest in the head region. 482 00:27:10,190 --> 00:27:12,670 There they come from both neural crest 483 00:27:12,670 --> 00:27:14,570 and from what we call placodes. 484 00:27:14,570 --> 00:27:16,590 It's thickening of the ectoderm that 485 00:27:16,590 --> 00:27:20,270 happens due to other inductive influences. 486 00:27:20,270 --> 00:27:22,650 Not the notochord now. 487 00:27:22,650 --> 00:27:25,390 It can also come from peripheral nervous system. 488 00:27:25,390 --> 00:27:28,790 But here in the spinal cord, it all 489 00:27:28,790 --> 00:27:32,030 comes from the neural crest. 490 00:27:32,030 --> 00:27:34,970 And then there's a few names you should learn. 491 00:27:34,970 --> 00:27:39,460 When this tube forms, note I show here the tube 492 00:27:39,460 --> 00:27:41,190 is already getting a little thicker. 493 00:27:41,190 --> 00:27:43,500 There are cells proliferating there. 494 00:27:43,500 --> 00:27:47,390 They proliferate in the sides of the tube, 495 00:27:47,390 --> 00:27:51,280 not at the very top and the very bottom. 496 00:27:51,280 --> 00:27:53,270 The very top is called the roof plate. 497 00:27:53,270 --> 00:27:56,120 It remains one cell thick. 498 00:27:56,120 --> 00:27:57,662 And the bottom is the floor plate. 499 00:27:57,662 --> 00:28:01,910 It also remains one cell thick, right to the adult. 500 00:28:01,910 --> 00:28:04,350 But the walls get thicker and thicker. 501 00:28:04,350 --> 00:28:10,020 And in development the ventral part closest to the notochord 502 00:28:10,020 --> 00:28:14,440 tends to proliferate a little bit faster. 503 00:28:14,440 --> 00:28:16,980 That's where the motor neurons will form. 504 00:28:16,980 --> 00:28:21,320 So we call the upper part here the alar plate. 505 00:28:21,320 --> 00:28:24,840 And the lower part the basal plate. 506 00:28:24,840 --> 00:28:28,160 And little groove separating the two 507 00:28:28,160 --> 00:28:31,390 is called the sulcus limitans, the limiting sulcus. 508 00:28:31,390 --> 00:28:33,960 And we'll see pictures of that as we go on. 509 00:28:43,770 --> 00:28:47,030 Let me show you some pictures of it. 510 00:28:47,030 --> 00:28:51,740 We mentioned this already, the discovery of induction. 511 00:28:51,740 --> 00:28:53,950 Where does that closure begin? 512 00:28:53,950 --> 00:28:55,190 Remember, it's a groove. 513 00:28:55,190 --> 00:28:58,670 It's a neural groove all along the back of the organism. 514 00:28:58,670 --> 00:29:07,050 And then it forms a tube, as you see in this picture. 515 00:29:07,050 --> 00:29:09,905 Well, where does this first begin? 516 00:29:16,665 --> 00:29:20,640 So I show you this picture. 517 00:29:20,640 --> 00:29:22,460 It begins sort of in the middle. 518 00:29:22,460 --> 00:29:24,840 This is the head, this is rostral. 519 00:29:24,840 --> 00:29:27,780 This is the caudal end here. 520 00:29:27,780 --> 00:29:30,420 That's where the neural tube is first closing. 521 00:29:30,420 --> 00:29:32,420 So if we go further back or further forward, 522 00:29:32,420 --> 00:29:33,600 it would look like this. 523 00:29:33,600 --> 00:29:36,630 It would be a neural groove still. 524 00:29:36,630 --> 00:29:38,390 So it starts to close. 525 00:29:38,390 --> 00:29:42,060 That region corresponds to the cervical region 526 00:29:42,060 --> 00:29:45,950 of the spinal cord, the upper part, or the most rostral part 527 00:29:45,950 --> 00:29:47,820 of the spinal cord. 528 00:29:47,820 --> 00:29:51,350 That's where development is a little more advanced. 529 00:29:51,350 --> 00:29:53,240 That's where the neural tube first closes. 530 00:29:58,450 --> 00:30:02,110 So the last region to close, as you can guess, it sort of 531 00:30:02,110 --> 00:30:06,690 zips up this way and zips up caudally, the very tail region 532 00:30:06,690 --> 00:30:07,580 here. 533 00:30:07,580 --> 00:30:09,280 The last part to close. 534 00:30:09,280 --> 00:30:16,385 And similarly, the most rostral part of the CNS, the last part 535 00:30:16,385 --> 00:30:17,270 to close. 536 00:30:17,270 --> 00:30:21,110 So if some abnormality occurs during early development, 537 00:30:21,110 --> 00:30:26,360 and it does happen, you can get a failure to completely close. 538 00:30:26,360 --> 00:30:29,270 When it doesn't close caudally here, 539 00:30:29,270 --> 00:30:31,440 you get a condition known as spina bifida. 540 00:30:34,210 --> 00:30:36,870 That can be corrected surgically. 541 00:30:36,870 --> 00:30:41,040 But when it fails to close rostrally, 542 00:30:41,040 --> 00:30:47,960 there's a failure of the forebrain to develop. 543 00:30:47,960 --> 00:30:50,090 You call it anencephaly. 544 00:30:50,090 --> 00:30:54,350 Basically it means without a brain. 545 00:30:54,350 --> 00:30:55,790 They do have some brain. 546 00:30:55,790 --> 00:30:58,020 They have the brainstem. 547 00:30:58,020 --> 00:31:02,650 And babies that are born that way don't live very long. 548 00:31:02,650 --> 00:31:07,490 It's impossible to repair that. 549 00:31:07,490 --> 00:31:10,540 They've been studied a little bit 550 00:31:10,540 --> 00:31:14,830 in their brief, very brief lives. 551 00:31:14,830 --> 00:31:16,810 Let's take a look at that happening. 552 00:31:31,580 --> 00:31:34,590 These are interesting animations that you can actually 553 00:31:34,590 --> 00:31:36,400 find on the web. 554 00:31:36,400 --> 00:31:39,920 If you look at the cross section up here-- don't take notes now, 555 00:31:39,920 --> 00:31:40,830 look up here. 556 00:31:40,830 --> 00:31:43,530 Look up here. 557 00:31:43,530 --> 00:31:46,220 Look at the screen or you're missing the main show. 558 00:31:51,020 --> 00:31:55,120 You see the neural tube in the 3D picture there closing. 559 00:31:55,120 --> 00:31:57,620 You see what's happening up there. 560 00:31:57,620 --> 00:31:59,990 The black dots are the neural crest cells 561 00:31:59,990 --> 00:32:02,460 that are staying on the outside. 562 00:32:02,460 --> 00:32:04,350 They don't get incorporated. 563 00:32:04,350 --> 00:32:08,790 The tube closes without them. 564 00:32:08,790 --> 00:32:15,440 The red is the mesoderm, mostly muscle tissue there. 565 00:32:15,440 --> 00:32:19,840 And the vertebrae are forming around the neural tube. 566 00:32:22,570 --> 00:32:28,470 So that's where you find the peripheral ganglia 567 00:32:28,470 --> 00:32:30,010 of the sympathetic nervous system. 568 00:32:30,010 --> 00:32:33,090 And there's the dorsal root ganglia. 569 00:32:33,090 --> 00:32:34,760 What are these out here? 570 00:32:34,760 --> 00:32:36,410 They're the neural crest cells. 571 00:32:36,410 --> 00:32:39,030 I didn't mention those before. 572 00:32:39,030 --> 00:32:42,620 They're migrating into the skin, mostly 573 00:32:42,620 --> 00:32:46,183 melanocytes, the pigmented cells in the skin. 574 00:32:53,000 --> 00:32:54,690 Rather than look at that again, I 575 00:32:54,690 --> 00:32:58,980 want to show you an actual photograph of neurulation 576 00:32:58,980 --> 00:33:01,030 in the clawed frog, the Xenopus. 577 00:33:03,740 --> 00:33:07,430 It happens very fast, so we'll look at it several times. 578 00:33:07,430 --> 00:33:14,220 If you just focus on one of these, 579 00:33:14,220 --> 00:33:18,660 you see the whole thing because they've speeded it up so much. 580 00:33:18,660 --> 00:33:21,760 With the formation you don't really see the neural plate, 581 00:33:21,760 --> 00:33:26,962 but you see the neural groove forming and you see it close. 582 00:33:26,962 --> 00:33:30,720 It zips up rostrally and caudally. 583 00:33:30,720 --> 00:33:33,500 And then the embryo turns a little bit 584 00:33:33,500 --> 00:33:36,560 so it looks a little bit more like the end of this one. 585 00:33:42,530 --> 00:33:44,705 You can find those, if you do some searching. 586 00:33:44,705 --> 00:33:47,270 You can find them online. 587 00:33:47,270 --> 00:33:51,850 This is just a picture of that early stage, taken 588 00:33:51,850 --> 00:33:53,340 with the electron microscope when 589 00:33:53,340 --> 00:33:55,930 they used a method called freeze-fracture. 590 00:33:55,930 --> 00:33:57,440 They freeze it solid. 591 00:33:57,440 --> 00:34:03,080 And then if they could get it to break along this line, 592 00:34:03,080 --> 00:34:08,159 you can see individual cells in both the CNS 593 00:34:08,159 --> 00:34:12,570 there in the neural tube, and the mesoderm and the ectoderm. 594 00:34:12,570 --> 00:34:16,350 And then you see the endoderm down here. 595 00:34:16,350 --> 00:34:18,580 And this just shows what it's like in humans 596 00:34:18,580 --> 00:34:24,655 at particular stages, 22 and 24 days after conception. 597 00:34:27,389 --> 00:34:31,204 I picked this because it's right after the neural tube starts 598 00:34:31,204 --> 00:34:32,370 to close. 599 00:34:32,370 --> 00:34:35,666 In the hamster, that I've used a lot, 600 00:34:35,666 --> 00:34:40,630 it closes on the eighth day after conception. 601 00:34:40,630 --> 00:34:44,040 So it can happen in some species very, very fast. 602 00:34:44,040 --> 00:34:47,359 Of course, they're much smaller too. 603 00:34:47,359 --> 00:34:49,820 It tends to be slower in the larger animals. 604 00:34:54,739 --> 00:34:57,700 So what is this term, sonic hedgehog? 605 00:34:57,700 --> 00:35:01,290 We're not going back to comparative neurology here. 606 00:35:01,290 --> 00:35:03,433 It's the name for what? 607 00:35:03,433 --> 00:35:04,308 AUDIENCE: [INAUDIBLE] 608 00:35:10,160 --> 00:35:16,120 PROFESSOR: It's a particular molecule, sonic hedgehog. 609 00:35:16,120 --> 00:35:19,510 It's just the name for a protein, a molecule. 610 00:35:22,090 --> 00:35:23,880 It actually has a number of roles 611 00:35:23,880 --> 00:35:25,760 in the formation of the nervous system. 612 00:35:25,760 --> 00:35:28,480 Where's it come from in this process 613 00:35:28,480 --> 00:35:32,590 we're starting right now? 614 00:35:32,590 --> 00:35:35,620 I told you before, where the induction comes from. 615 00:35:40,370 --> 00:35:41,710 The notochord. 616 00:35:41,710 --> 00:35:47,210 Sonic hedgehog is generated by the notochord. 617 00:35:47,210 --> 00:35:49,860 It induces the formation of the nervous system, 618 00:35:49,860 --> 00:35:51,880 and does other things too. 619 00:35:51,880 --> 00:35:57,500 And if we look at this picture, they're 620 00:35:57,500 --> 00:36:04,300 coming-- these would be where the molecules are. 621 00:36:04,300 --> 00:36:07,110 Of course, they're probably going all around. 622 00:36:07,110 --> 00:36:12,920 I'm showing the ones that are in a concentrated way affecting 623 00:36:12,920 --> 00:36:14,650 these cells above it. 624 00:36:14,650 --> 00:36:17,210 But still coming there. 625 00:36:17,210 --> 00:36:21,525 And it's affecting this lower part of the cord. 626 00:36:21,525 --> 00:36:24,780 It serves as a ventralizing influence. 627 00:36:24,780 --> 00:36:29,810 It makes that ventral part of the neural tube-- see, 628 00:36:29,810 --> 00:36:31,700 they're still here. 629 00:36:31,700 --> 00:36:35,690 It makes the cells here form differently than the cells 630 00:36:35,690 --> 00:36:37,520 up here. 631 00:36:37,520 --> 00:36:40,460 Without sonic hedgehog and its ventralizing influence, 632 00:36:40,460 --> 00:36:43,180 you wouldn't get to form early differentiation of motor 633 00:36:43,180 --> 00:36:45,380 neurons. 634 00:36:45,380 --> 00:36:49,070 What about the dorsal part? 635 00:36:49,070 --> 00:36:53,660 There are inductive influences on this part, 636 00:36:53,660 --> 00:36:56,960 the part that came from way out here. 637 00:36:56,960 --> 00:37:00,930 It forms the dorsal part of the cord. 638 00:37:00,930 --> 00:37:06,330 Those inductive influences came from the ectoderm. 639 00:37:06,330 --> 00:37:08,590 And I mention it here. 640 00:37:08,590 --> 00:37:11,300 The dorsalizing factors are secreted 641 00:37:11,300 --> 00:37:15,266 by the ectoderm adjacent to the neural tube. 642 00:37:15,266 --> 00:37:20,220 The main ones are this BMP-4 and 7. 643 00:37:20,220 --> 00:37:23,630 BMP actually means bone morphogenetic protein, 644 00:37:23,630 --> 00:37:27,665 because it has a role in bone formation as well. 645 00:37:27,665 --> 00:37:29,866 And now we're talking about its influence 646 00:37:29,866 --> 00:37:31,370 on the nervous system. 647 00:37:31,370 --> 00:37:35,050 So it induces changes in the dorsal part of the cord. 648 00:37:37,980 --> 00:37:41,000 It causes those cells to develop differently 649 00:37:41,000 --> 00:37:43,940 than the ones ventrally. 650 00:37:43,940 --> 00:37:45,620 That leaves a lot of things unexplained. 651 00:37:45,620 --> 00:37:48,216 But at least it was a start in looking 652 00:37:48,216 --> 00:37:51,360 at how the nervous system develops. 653 00:37:51,360 --> 00:37:53,610 Now I want to talk about cell division. 654 00:37:53,610 --> 00:37:56,760 What are the two main types of cell division 655 00:37:56,760 --> 00:37:58,440 that I described in this chapter? 656 00:38:01,860 --> 00:38:03,800 There are differences in cell division 657 00:38:03,800 --> 00:38:08,480 that make a huge difference in h how the nervous system forms. 658 00:38:08,480 --> 00:38:11,290 Symmetric and asymmetric. 659 00:38:11,290 --> 00:38:14,567 And for that, you need to look at a picture like this. 660 00:38:14,567 --> 00:38:15,525 This is the cell cycle. 661 00:38:19,550 --> 00:38:22,170 The cell here moves away from the ventricle. 662 00:38:22,170 --> 00:38:23,870 But when I say the cell, I really 663 00:38:23,870 --> 00:38:25,820 mean the nucleus of the cell. 664 00:38:25,820 --> 00:38:31,270 Because it's attached to the pia out here, 665 00:38:31,270 --> 00:38:34,210 to the ventricle here. 666 00:38:34,210 --> 00:38:36,780 But it moves away from the ventricle 667 00:38:36,780 --> 00:38:39,310 in order to synthesize its DNA. 668 00:38:39,310 --> 00:38:44,450 It moves towards the ventricle in order to undergo mitosis. 669 00:38:44,450 --> 00:38:48,905 And it can undergo mitosis with a symmetric split 670 00:38:48,905 --> 00:38:52,330 or an asymmetric split. 671 00:38:52,330 --> 00:38:54,970 When it splits symmetrically, it tends 672 00:38:54,970 --> 00:39:00,830 to split along a line that's at right angles 673 00:39:00,830 --> 00:39:03,920 to ventricular surface. 674 00:39:03,920 --> 00:39:07,870 And when it does that, the distribution of proteins 675 00:39:07,870 --> 00:39:12,960 in the cell-- there's two proteins in particular-- 676 00:39:12,960 --> 00:39:17,200 tends to be pretty even in the two daughter cells. 677 00:39:17,200 --> 00:39:21,930 So the two daughter cells will behave pretty similar. 678 00:39:21,930 --> 00:39:26,930 Basically, they remain stem cells, they keep dividing. 679 00:39:26,930 --> 00:39:30,610 But when it splits asymmetrically, 680 00:39:30,610 --> 00:39:34,690 you end up with a very uneven distribution of those proteins. 681 00:39:34,690 --> 00:39:36,070 Notch and numb they're called. 682 00:39:38,750 --> 00:39:42,000 And now you get the two cells behaving differently. 683 00:39:42,000 --> 00:39:43,575 One remains a stem cell. 684 00:39:43,575 --> 00:39:45,010 It keeps dividing. 685 00:39:45,010 --> 00:39:49,390 The other one becomes post-mitotic 686 00:39:49,390 --> 00:39:51,170 and does something very differently. 687 00:39:51,170 --> 00:39:53,850 It migrates away. 688 00:39:53,850 --> 00:39:57,100 And in many cases the migration is simply, 689 00:39:57,100 --> 00:39:58,820 like over here on the cell cycle, 690 00:39:58,820 --> 00:40:03,040 the nucleus just moves away from the ventricle. 691 00:40:03,040 --> 00:40:04,100 It can be doing that. 692 00:40:04,100 --> 00:40:06,480 The attachments can remain. 693 00:40:06,480 --> 00:40:08,790 Cajal saw things like this. 694 00:40:11,960 --> 00:40:14,780 These are the way they look in Golgi in many cases. 695 00:40:14,780 --> 00:40:16,730 You might have been looking at two cells here. 696 00:40:16,730 --> 00:40:22,070 But in some cases they might be cells with two nuclei. 697 00:40:22,070 --> 00:40:26,430 Here's a cell that's lost its external process. 698 00:40:26,430 --> 00:40:29,930 All of these in here, they've regained the attachment 699 00:40:29,930 --> 00:40:31,770 to the pia. 700 00:40:31,770 --> 00:40:35,050 And when the nucleus just moves further and further 701 00:40:35,050 --> 00:40:39,370 from the ventricle and never returns, we say it's migrating. 702 00:40:39,370 --> 00:40:45,330 We say it's migrating by nuclear translocation, the first type 703 00:40:45,330 --> 00:40:47,850 of migration. 704 00:40:47,850 --> 00:40:50,040 Here's his picture of the chick spinal cord 705 00:40:50,040 --> 00:40:53,520 on the third day of incubation. 706 00:40:53,520 --> 00:40:54,765 Chicks grow very fast. 707 00:40:54,765 --> 00:40:57,404 They're a favorite among embryologists 708 00:40:57,404 --> 00:40:59,320 because you can cut a little window in the egg 709 00:40:59,320 --> 00:41:01,111 and you can look at these things happening. 710 00:41:03,620 --> 00:41:06,470 And note that some of the cells are right near the ventricle. 711 00:41:06,470 --> 00:41:09,990 But all of them that he shows in this particular picture 712 00:41:09,990 --> 00:41:11,570 are attached to the pia. 713 00:41:15,070 --> 00:41:18,800 So it's really similar to roof plate and floor plate there. 714 00:41:18,800 --> 00:41:21,669 It's just that this has a lot longer here 715 00:41:21,669 --> 00:41:22,710 and there's more of them. 716 00:41:26,430 --> 00:41:32,490 Well, if you look at other day three pictures, 717 00:41:32,490 --> 00:41:36,010 let's just look at that right now. 718 00:41:36,010 --> 00:41:37,495 Here's another day three picture. 719 00:41:40,340 --> 00:41:42,840 Golgi is selective. 720 00:41:42,840 --> 00:41:46,120 Sometimes you're getting more advanced cells, when you're 721 00:41:46,120 --> 00:41:47,970 looking at developing animals, sometimes 722 00:41:47,970 --> 00:41:52,990 you're getting the early developing cells. 723 00:41:52,990 --> 00:41:57,110 But you see on that same day, perhaps later in the day, 724 00:41:57,110 --> 00:42:03,780 he was able to identify ventral and dorsal roots forming. 725 00:42:03,780 --> 00:42:06,620 How did he do that? 726 00:42:06,620 --> 00:42:10,890 By recognizing something that he was probably 727 00:42:10,890 --> 00:42:12,110 the first to recognize. 728 00:42:12,110 --> 00:42:14,346 And he named them. 729 00:42:14,346 --> 00:42:18,510 The active growing tips that we call a growth cone, 730 00:42:18,510 --> 00:42:21,620 processes extending out. 731 00:42:21,620 --> 00:42:24,239 And when he saw that happening here, 732 00:42:24,239 --> 00:42:25,780 and he looked at them a little older, 733 00:42:25,780 --> 00:42:28,360 he would see the growth cones further away. 734 00:42:28,360 --> 00:42:31,390 He could see that an axon was growing, 735 00:42:31,390 --> 00:42:34,300 forming a ventral root. 736 00:42:34,300 --> 00:42:40,490 He started seeing that in day three of the chick. 737 00:42:40,490 --> 00:42:45,620 He also saw growth cones begin in the developing spinal cord. 738 00:42:45,620 --> 00:42:51,590 And here he saw some of those cells of the neural crest that 739 00:42:51,590 --> 00:42:56,720 weren't in the CNS, he saw them with two growth cones. 740 00:42:56,720 --> 00:42:59,180 One growing out towards the periphery. 741 00:42:59,180 --> 00:43:06,187 Another one growing right into the neural tube. 742 00:43:08,756 --> 00:43:11,280 And that was Cajal's work. 743 00:43:11,280 --> 00:43:16,720 So here I'm asking how did neural scientists come 744 00:43:16,720 --> 00:43:20,660 to know that there at least two major modes of cell migration 745 00:43:20,660 --> 00:43:23,550 in the embryonic [INAUDIBLE]? 746 00:43:23,550 --> 00:43:25,990 Here's what happened. 747 00:43:25,990 --> 00:43:28,390 I just described nuclear translocation 748 00:43:28,390 --> 00:43:34,596 as a type of migration, like this picture here. 749 00:43:34,596 --> 00:43:38,570 When these cells are moving like this one, it's moved very far, 750 00:43:38,570 --> 00:43:40,950 it's moved way out towards the pial surface. 751 00:43:40,950 --> 00:43:44,220 It never comes back because it's not in the cell cycle anymore, 752 00:43:44,220 --> 00:43:46,470 yet we say it's migrated. 753 00:43:46,470 --> 00:43:50,314 And eventually it loses its process. 754 00:43:50,314 --> 00:43:53,080 It usually uses both of its attachments, 755 00:43:53,080 --> 00:43:55,710 to the pia on the one side and to the ventricle on the other. 756 00:43:58,510 --> 00:44:02,325 That had been described, had been seen by Cajal. 757 00:44:02,325 --> 00:44:05,930 It was described by Kent Morest, who was at Harvard 758 00:44:05,930 --> 00:44:09,490 and then moved to the University of Connecticut. 759 00:44:09,490 --> 00:44:14,090 And then a man named Pasko Rakic, also at Harvard, 760 00:44:14,090 --> 00:44:17,736 but then he moved to Yale, he worked 761 00:44:17,736 --> 00:44:19,110 on a different part of the brain. 762 00:44:19,110 --> 00:44:20,820 He worked on primates. 763 00:44:20,820 --> 00:44:25,720 He discovered evidence that in primates that 764 00:44:25,720 --> 00:44:28,050 is not how cells migrate. 765 00:44:28,050 --> 00:44:31,410 They attach to a glial cell that was elongated. 766 00:44:31,410 --> 00:44:34,310 And they used the glial cell sort of as a ladder, 767 00:44:34,310 --> 00:44:36,390 and they moved along it. 768 00:44:36,390 --> 00:44:39,111 So he said that's the way cells from the central nervous system 769 00:44:39,111 --> 00:44:39,610 migrate. 770 00:44:39,610 --> 00:44:42,890 And there actually became a sort of a conflict between these two 771 00:44:42,890 --> 00:44:43,665 views. 772 00:44:43,665 --> 00:44:45,430 Which was really silly. 773 00:44:45,430 --> 00:44:47,180 Because as you might expect, both occur. 774 00:44:50,160 --> 00:44:54,280 And I want you to know how that argument was settled. 775 00:44:57,090 --> 00:45:00,950 By proof that nuclear translocation 776 00:45:00,950 --> 00:45:04,435 is not just in the spinal cord, but right in the brain. 777 00:45:04,435 --> 00:45:07,910 It can be the major mode of movement. 778 00:45:10,910 --> 00:45:13,030 Now we know there's other kinds of cell movement 779 00:45:13,030 --> 00:45:14,945 too, among other substrate factors. 780 00:45:14,945 --> 00:45:17,140 But we're just gonna talk about this. 781 00:45:17,140 --> 00:45:20,320 And we'll talk more about guidance by radial glial cells 782 00:45:20,320 --> 00:45:24,720 much later when we talk about development of cortex. 783 00:45:24,720 --> 00:45:31,610 But let's talk about a study by these two people, Morest 784 00:45:31,610 --> 00:45:35,065 and Valerie Domesick, who was a student [INAUDIBLE] here 785 00:45:35,065 --> 00:45:39,240 at MIT that went to work with Morest. 786 00:45:39,240 --> 00:45:43,010 This will be just briefly the last topic. 787 00:45:43,010 --> 00:45:47,030 They were studying a cell in the tectum 788 00:45:47,030 --> 00:45:48,660 that was very interesting. 789 00:45:48,660 --> 00:45:53,390 Because if you look at the adult, 790 00:45:53,390 --> 00:45:55,430 you would see the cell and its dendrites 791 00:45:55,430 --> 00:45:58,430 here near the surface of the tectum. 792 00:45:58,430 --> 00:46:02,280 The initial part of this axon had this peculiar bend 793 00:46:02,280 --> 00:46:05,490 that looks like the crook in a shepherd's staff. 794 00:46:05,490 --> 00:46:09,340 So it was called the Shepherd's Crook Cell. 795 00:46:09,340 --> 00:46:11,160 That was the name of it. 796 00:46:11,160 --> 00:46:13,720 They looked at earlier and earlier periods. 797 00:46:13,720 --> 00:46:15,720 They kept seeing the crook. 798 00:46:15,720 --> 00:46:19,640 But they found the period where the axon was just 799 00:46:19,640 --> 00:46:20,865 beginning to form. 800 00:46:20,865 --> 00:46:23,430 It had the peculiar bend. 801 00:46:23,430 --> 00:46:25,660 There's the growth cone. 802 00:46:25,660 --> 00:46:28,910 And then they saw that at that stage 803 00:46:28,910 --> 00:46:32,812 the cell body was way down here, near the ventricle. 804 00:46:32,812 --> 00:46:35,930 The cell body hadn't moved yet. 805 00:46:35,930 --> 00:46:37,590 It hadn't migrated. 806 00:46:37,590 --> 00:46:40,910 And yet the axon was already forming. 807 00:46:40,910 --> 00:46:44,800 So you have to realize that the cell extends all the way 808 00:46:44,800 --> 00:46:47,470 from ventricle to the midbrain surface here. 809 00:46:47,470 --> 00:46:51,610 The axon is forming here, long before the cell body is there. 810 00:46:51,610 --> 00:46:57,320 And then the cell body is moving, as you see here. 811 00:46:57,320 --> 00:47:01,890 And finally it gets to the point where the axon originates. 812 00:47:01,890 --> 00:47:06,390 They looked at many embryos closely spaced in age 813 00:47:06,390 --> 00:47:08,990 and they saw all these changes. 814 00:47:08,990 --> 00:47:11,665 And they reported it at the American Association 815 00:47:11,665 --> 00:47:14,380 of Anatomists meeting, where a group 816 00:47:14,380 --> 00:47:22,780 called the Cajal Club met. 817 00:47:22,780 --> 00:47:25,740 It was a favorite meeting of neuroanatomists at that time. 818 00:47:25,740 --> 00:47:28,450 It was before there was a society for neuroscience. 819 00:47:28,450 --> 00:47:29,825 But their talk was so convincing, 820 00:47:29,825 --> 00:47:31,110 and Rakic was there. 821 00:47:31,110 --> 00:47:32,970 He agreed afterwards, OK, there's 822 00:47:32,970 --> 00:47:34,860 gotta be at least two kinds of migration. 823 00:47:34,860 --> 00:47:36,325 Because I know that that's not how 824 00:47:36,325 --> 00:47:39,200 it happens in the neocortex. 825 00:47:39,200 --> 00:47:42,737 So that's the story of how we became more certain that there 826 00:47:42,737 --> 00:47:44,320 were two different kinds of migration. 827 00:47:46,860 --> 00:47:49,195 So that's where we're gonna stop today. 828 00:47:52,110 --> 00:47:55,610 We've already talked about this. 829 00:47:55,610 --> 00:47:58,320 I guess we've finished, except for review. 830 00:47:58,320 --> 00:47:59,740 So I'll post these slides. 831 00:47:59,740 --> 00:48:01,430 You can go over them. 832 00:48:01,430 --> 00:48:05,380 And we'll be able to talk about the next chapter 833 00:48:05,380 --> 00:48:08,630 about spinal cord on Friday.