Organizing the Embryo: The Central Nervous System

In the embryonic development of a zygote, gradients of mRNAs and proteins, deposited in the egg by the mother as she formed it, give rise to cells of diverse fates despite their identical genomes.

For a discussion of the evidence that leads to this important conclusion, examine Embryonic Development: Getting Started.

But is the embryo fully patterned in the fertilized egg? It is difficult to imagine that the relatively simple gradients in the egg could account for all the complex migration and differentiation of cells during embryonic development. And, in fact, the answer is no. However, once these gradients have sent certain cells along a particular path of gene expression, the stage is set for those cells to begin influencing nearby cells to become increasingly diversified.

In other words,

The Organizer

In 1924, the German embryologists Hans Spemann and Hilde Mangold performed an experiment that Spemann and Mangold knew that the cells that develop in the region of the gray crescent migrate into the embryo during gastrulation and form the notochord (the future backbone; made of mesoderm).

They cut out a piece of tissue from the gray crescent region of one newt gastrula and transplanted it into the ventral side of a second newt gastrula. To make it easier to follow the fate of the transplant, they used the embryo of one variety of newt as the donor and a second variety as the recipient.

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The remarkable results:

But the most remarkable finding of all was that the neural folds were built from recipient cells, not donor cells. In other words, the transplant had altered the fate of the overlying cells (which normally would have ended up forming skin [epidermis] on the side of the animal) so that they produced a second head instead! Spemann and Mangold used the term induction for the ability of one group of cells to influence the fate of another. And because of the remarkable inductive power of the gray crescent cells, they called this region the organizer.

Over the next three quarters of a century, vigorous searches have been made to identify the molecules liberated by the organizer that induce overlying cells to become nerve tissue. One candidate after another has been put forward and then found not to be responsible. Part of the problem has been that not until just recently has it become clear that the organizer This is how it works:

Patterning the central nervous system in Drosophila

Remarkably, it turns out that proteins similar in structure to the bone morphogenetic proteins and also to chordin are found in Drosophila. In fact, these proteins and their mRNAs are completely interchangeable!
A selection of antagonistic pairs of proteins that guide the patterning of the embryo.
XenopusBone Morphogenetic Protein-4 (BMP-4)blocked by chordin
and also by noggin
Drosophila Decapentaplegic (DPP)blocked by short gastrulation (SOG)
and also by a noggin homolog?
Mammalseveral BMPsblocked by ?

Dorsal vs Ventral Nerve Cords

Although their actions are similar, the distribution of these proteins in Drosophila differs from that in Xenopus (as well as in mammals and other vertebrates).

In Drosophila, However, their actions on overlying cells are the same as in Xenopus; that is, the sog protein prevents the dpp protein from blocking the formation of the central nervous system. The result in Drosophila is that its central nervous system forms on the ventral side of the embryo, not on the dorsal! And, you may remember that one of the distinguishing traits of all arthropods (insects, crustaceans, arachnids) as well as many other invertebrates, such as the annelid worms, is a ventral nerve cord. Vertebrates have a dorsal (spinal) nerve cord.

Patterning in Mammals

The establishment of the dorsal central nervous system probably occurs in mammals by mechanisms similar to those in Xenopus. Close relatives (homologs) of the Xenopus molecules occur in mammals. In fact, the BMPs were discovered in mammalian tissue before they were found in Xenopus (and have many important functions throughout the life of the animal). Similarly, the Wnt molecules (see below) found in Xenopus were first identified in mammals (as the product of oncogenes).

Redundancy in patterning

The patterning of the embryo employs a number of redundant, or at least overlapping, mechanisms. (In fact, genetic redundancy seems to be a key feature of life. It is the reason that knockout mice are so often able to function without certain genes).

The table below gives another set of antagonistic pairs of molecules:
Another set of antagonistic pairs of proteins that guide the patterning of the embryo.
XenopusXwnt-8Xfrzb-1
Drosophilawingless (wg)frizzled
Mammalvarious Wnt oncoproteinsfrzb-1 ("frizbee")

Once again, the molecules in one column are close relatives, even though many millions of years have passed since the ancestors of these animals took separate evolutionary paths!

We're half-way done!

Xenopus development (and probably that of animals in general) passes through three rather different (although often overlapping) phases:
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23 June 1999