Basics: Neurulation

When we had last seen our basic embryo, it had gone through gastrulation — a process in which cells of a two-layered sheet had moved inward, setting up the three germ layers (endoderm, mesoderm, and ectoderm) of the early embryo. In particular, cells at the organizer, a tissue that induces or organizes migrating cells, had rolled inwards to set up specific axial mesoderm structures: the prechordal plate, which will underlie cranial structures, and the notochord, which resides under the future hindbrain and spinal cord. At this point, the embryo has an outer layer of ectoderm, and lying under part of it, a band of prechordal mesoderm and notochord. In addition, the ectoderm is loaded with a molecule called BMP-4, a member of the TGF-β family of signaling molecules, and under its influence will go on to make skin, not nervous system. So what next?

In the absence of BMP-4, the ectoderm will instead become neuralized: it will make nervous system derivatives rather than skin. The organizer and that band of axial mesoderm are secreting molecules that inactivate BMP-4, called noggin, chordin, and follistatin (Wnt-3a and FGF are also important in more caudal regions of the nervous system). What we have is a system where all of the ectoderm is instructed to make skin, but one discrete stripe of mesoderm is emitting a signal to the ectoderm directly above it, overriding that instruction and encouraging the ectoderm to make a parallel stripe of neural tissue, instead.

The first overt response of the ectodermal tissue is for the cells to change shape. At this point, the ectoderm is a continuous sheet, where the cells are adherent to one another in a single layer; they are going to undergo coordinated shape changes to drive movement as a whole. All of the cells first become columnar, as you can see in the second diagram in this series, forming a neural plate:

i-86c8081d6c3235b5b39efd61f320d83a-neurulation2.gif

Cells then change from a columnar shape to forming an apical constriction on the dorsal side—this shape change causes the sheet to buckle and bend inwards (there's also a pattern of cell migration by ectodermal cells towards the dorsal midline that also puts pressure on the neural plate to fold). The sheet of neural cells rolls up until its edges meet, making a neural tube. The fluid filled space in the middle will become the central canal of the spinal cord and the ventricles of the brain.

The diagram below illustrates that there are some subtle differences in different animals. Amphibians, reptiles, birds, and mammals all make a lovely and obvious tube when they fold up, but fish are a little less overt—their neural cells are tightly adherent and don't expose a space as they fold, although the cell movements are very similar. They secondarily cavitate to form the essential central canal. This diagram illustrates another critical phenomenon, though: what happens at the dorsal seam, where the edges of the folding tube meet?

i-fa578dbd2b22433d1a44666352cb192f-neurulation1.jpg

At the edges of that dorsal midline, cells have to sort themselves out. Some will stick to the non-neural ectoderm and separate from the neural ectoderm, and form the epidermal epithelium. Others will stick with the neural ectoderm, and become part of the neural tube epithelium. Of unusual significance, though, are some in-between cells that are sort of 'left over' when the two epithelial sheets separate—they form a loose aggregate in the space between the skin and the neural tube, and have some unique properties. These are called neural crest cells, and at some time I'm going to have to write a Basics post just about them. They are a fascinating and important set of plastic cells that have great roles to play in both chordate development and evolution.

The closure of the neural tube is a critical point in development, and failures are depressingly common, occurring in about 1 in a thousand human births. Along the length of the mammalian nervous system, the tube typically closes up at a couple of points first, and then zippers itself up in between. If the edges fail to meet and fuse, the tube remains open to the external environment, which is most definitely not good. If the posterior end fails to close, the condition is called spina bifida. Spina bifida affects individuals to varying degrees depending on how much of the tube is left open; neural tube exposure is associated with nervous tissue damage in the affected area of the spinal cord, leading to anything from minor loss of sensation in the lower limbs to complete paralysis.

Failure of the anterior end of the neural tube is even more devastating. The fetal forebrain is exposed to the amniotic fluid, and fails to develop and degenerates, and the skull itself does not close over. This condition is called anencephaly, and it is lethal.

Assuming closure goes well, as it does most of the time, the end result is a hollow tube of neural epithelium suspended between an ectodermal epithelium dorsally and a notochord or prechordal plate ventrally. Signaling continues; remember that the epidermis is permeated with BMP4, and this BMP4 is going to induce a new signaling center in the neural tube, the roofplate, which is also going to secrete BMP4. Meanwhile, the notochord is also sending signals, and induces a floor plate in the ventral floor of the neural tube; the key molecule here is Sonic hedgehog, or Shh.

i-47b0bcda2e9c1182046e65f9eac90032-neurulation3.jpg

The double gradient — BMP4 spreading ventrally from the dorsal midline, Shh spreading dorsally from the ventral midline — sets up a pattern of regional specification, where the identity of neurons in the tube can be determined by just 'reading' the relative concentrations of the two factors. In addition, identity along the longitudinal axis is specified by the pattern of expression of the Hox genes. The process of neurulation sets aside a tube of tissue dedicated to forming the central nervous system, and establishes a dorsal-ventral and anterior-posterior coordinate system that allows cells to be parceled into unique fates.

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Neurulation is a series of cell movements and shape changes, inductive interactions, and changes in gene expression that partitions tissues into a discrete neural tube. It is one of those early and significant morphogenetic events that define an important tissue, in this case the nervous system,…
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That guy, John Wilkins, has been keeping a list of presentations of basic concepts in science, and he told me I'm supposed to do one on gastrulation. First I thought, no way—that's way too hard, and I thought this was all supposed to be about basic stuff. But then I figured that it can't be too…
The article about gastrulation from the other day was dreadfully vertebrate-centric, so let me correct that with a little addendum that mentions a few invertebrate patterns of gastrulation—and you'll see that the story hasn't changed. Remember, this is the definition of gastrulation that I…

Yeah, but which end becomes the radicle and which end becomes the shoot apex?

By Shaggy Maniac (not verified) on 22 Mar 2007 #permalink

Is this gonna be on the test?

By Tukla in Iowa (not verified) on 22 Mar 2007 #permalink

Thanks PZ! I love posts like these!

Is it true that in the most caudal part of the mammalian (and amphibian?) neural tube, the part that actually extends into the tail, neurulation is fish-style? Assuming that some adhesion molecule(s) are responsible for the fish/amphibian difference; does that also explain the tail/trunk difference in mammals, at least the mouse? Assuming that the fish method is older, have the amphibians (and mammals) 'simply' lost (some of) that adhesion molecule during evolution, perhaps only in the trunk? Would make a nice molecular evolution story.

Excellent post,
Very clear and concise. It's a shame I don't really get to learn all that much about this in psychology...

Seems like something I should know more about. Maybe in grad school?

Is this gonna be on the test?

Dude, if you don't complete Neurulation successfully, you'll end up
working for the Disco Institute.

So now we are, what, 20-30 days into the human gestation period? [Frantically googling.] (And how much is that in zebra fishes, btw? ;-)

Darn, this series of excellent posts will end too soon.

By Torbjörn Larsson (not verified) on 22 Mar 2007 #permalink

PZ - Thanks for the post. Nature is so amazing.

Dude, if you don't complete Neurulation successfully, you'll end up working for the Disco Institute.

Thank goodness nobody at work asked me to explain why I was laughing so hard.

By Reality Czech (not verified) on 23 Mar 2007 #permalink

Yeah, but which end becomes the radicle and which end becomes the shoot apex?

ROTFL!!!

By David Marjanović (not verified) on 23 Mar 2007 #permalink

well... do u guys think that mayb the evolution was 4 the better.. true some of the adhession mol might ve been lost, but then its evol to grow the limbs... like they say in the darwins theory, v dnt req a long head to foot spine, the signals r carried out otherwise, n v dnt need a tailbone either. ny ways .. think on terms where this period of gest faulters n the genes resp for NTD's

So now we are, what, 20-30 days into the human gestation period? [Frantically googling.] (And how much is that in zebra fishes, btw? ;-)

Darn, this series of excellent posts will end too soon.

By Torbjörn Larsson (not verified) on 22 Mar 2007 #permalink

Yeah, but which end becomes the radicle and which end becomes the shoot apex?

ROTFL!!!

By David Marjanović (not verified) on 23 Mar 2007 #permalink