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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 Spemann Organizer

In 1924, the Ph.D. student Hilde Mangold working in the laboratory of German embryologist Hans Spemann 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).

She 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, she used the embryo of one variety of newt as the donor and a second variety as the recipient.

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.

Link to another demonstration of induction performed by Spemann.

Ever since then, 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:

In the Spemann/Mangold experiment, transplanting an organizer to the ventral side provided a second source of chordin. This blocked BMP-4 binding to the overlying ectoderm and thus changed the fate of those cells to forming a second central nervous system rather than skin.

What Organizes the Organizer?

Protein synthesis by the cells of the organizer requires transcription of the relevant genes (e.g., chordin). Expression of organizer genes depends first on Wnt transcription factors. Their messenger RNAs were deposited by the mother in the vegetal pole of the egg. After fertilization and formation of the gray crescent, they

Its accumulation on the dorsal side of the embryo unleashes the activity of Nodal — a member of the Transforming Growth Factor-beta (TGF-β) family. Nodal induces these dorsal cells to begin expressing the proteins of Spemann's organizer.

A Tail Organizer

One of the distinguishing features of vertebrates is their tail, which extends out behind the anus.

French researchers have reported (in the 24 July 2003 issue of Nature) their discovery of a tail "organizer", that is, a cluster of cells in the embryo that induces nearby cells to contribute to the formation of the tail.

They worked with the zebrafish, Danio rerio (which also has a head organizer like that of newts).

They removed tiny clusters of cells from the ventral part of the blastula (a region roughly opposite where the Spemann-like organizer forms) and transplanted this into a region of the host embryo that would normally form flank.

The result: a second tail.

Using a fluorescent label, they were able to show that the extra tail was made not only from descendants of the transplanted cells but also from host cells that would normally have made flank.

Three proteins were essential:

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?

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. Chordates, including all vertebrates, have a dorsal (spinal) nerve cord.


We're halfway done!

Xenopus development (and probably that of animals in general) passes through three rather different (although often overlapping) phases:
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17 May 2011