Basics: Gastrulation

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 hard, after all, all you readers went through it successfully, and you even managed to do it before you developed a brain. So, sure, let's rattle this one off.

In the simplest terms, gastrulation is a stage in early development; in human beings it occurs between two and three weeks after fertilization. It is that stage when a two-layered cell mass undergoes a set of specific movements and interactions that establish the three germ layers of the embryo (endoderm, mesoderm, and ectoderm) and the beginnings of a three-dimensional structure. The end result doesn't look like much of an animal, but it has set up pools of cells that will contribute to specific future cell types, and has laid down the rough outline of tissues along the body axis.

During the blastula stage that precedes the gastrula, two important events occur. Cells divide repeatedly to generate a multicellular mass, but there isn't a lot of coordinated cell movements occurring, except that some sorting goes on into a mass or sheet on one side called the epiblast, and another called the hypoblast. That sets the stage: two sheets of cells are layered together.

Gastrulation follows. The definition of gastrulation by Wolpert is:

The process in animal embryos in which endoderm and mesoderm move from the outer surface of the embryo to the inside, where they give rise to internal organs.

What this means is that one layer of these sheets is going to dimple inward, and cells will flow inward, to the space between the two sheets. The cells that move into the interior will contribute to the endoderm (which eventually forms the lining of the gut) and the mesoderm (which will make muscle and connective tissue.) The cells that don't move inward form ectoderm, and will make skin and nervous tissue.

Here's what the process looks like in a cross section of a frog embryo. Blue is prospective ectoderm, yellow is prospective endoderm, and the orange cells are the developing mesoderm. In frogs, the cells roll in and under in a coherent sheet, a process called involution; in other animals, individual cells may lose adherence and migrate inward, a process called ingression. Either way, the result is the same, with cells finding their way into the interior to form new tissue layers.

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Another important aspect of the cell movements is that they generate new information and interact with the cells they pass to instruct or induce them to make other tissues. The cells migrating inward and rolling up along the dorsal side of the embryo are going to be allocated to specific, position and timing dependent fates. The first sets of cells moving inward are going to contribute to anterior mesoderm; the next form prechordal mesoderm, a tissue underlying cranial structures; and others will form the chordamesoderm, or notochord. These are important signaling centers. The notochord, for instance, is going to send signals to the strip of ectoderm directly above it, instructing it to form neural tissue. Interfere with that signal, and nothing forms but skin.

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That particular region where cells move inward forms the blastopore (eventually the anus) of the animal, and the cells in that region just above the opening are called the organizer. The organizer is so called because it is a focal site that has the property of 'organizing' all the migrating tissues, with the inward moving cells making that longitudinal distribution of fates from anterior mesoderm to pre-chordal mesoderm to chordamesoderm, and specifying the fates of other tissues along the way. Transplanting just that patch of organizer tissue to other regions of the gastrula is enough to trigger additional whole body axes, making twinned amphibians.

The diagrams above are all from frogs, which have large, yolky eggs that cleave, and produces a rather unusual (but very well studied!) gastrula. Other vertebrates look rather different; they form two sheets in a disc rather than the ball-like form of the amphibian, and cells delaminate or introgress at a site called Hensen's node (or just the node) and along a line called the primitive streak. The net effect is the same, though, with the migrating cells establishing endodermal and mesodermal tissues, interacting with each other and the ectoderm to specify tissues along the axis.

Birds and mammals, including us, all do it this way.

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Superficially, that looks very different from a frog: a frog embryo is a ball of cells with a point where it puckers inward and cells roll into the interior, while bird and mammal embryos form a flat two layered sheet, and cells dissociate and stream inward along a groove. One way we can confirm that these are actually homologous developmental processes is by examining the molecular pathways that underlie them.

Here is the array of genes active in the organizer in both the frog and the mouse. It's the same set of genes all over the place. (If you're wondering whether Xnr-3 and Nodal are at all similar…"Xnr" is short for "Xenopus Nodal related".)

The next stage in development after gastrulation is neurulation, when the most visible morphological change is the folding of the neural tube and development of the nervous system. The step after that is the pharyngula stage (hey, that name sounds familiar!) when the foundation of the body plan is laid down and the major organs all form.

(Figures are taken from Principles of Development^{(amzn/b&n/abe/pwll)} by Lewis Wolpert et al., a good general textbook on developmental biology.)