Genes and Morphology

For any organism, or organ within that organism, the component parts are in a specific, characteristic relationship to each other. This applies even at the level of single cells. Skin cells are on the outside, intestinal cells on the inside. How do these cells "know" what to do?

Every cell type adopts its particular "identity" by "turning on" a specific set of genes. Of the 30,000 or so genes in human chromosomes, each cell type expresses only a subset. It is the combination of genes that are used in a cell that gives it its particular characteristics. This means that cells don't "know" what to do; rather, the set of genes that they express makes them what they are. But, this just pushes the Difficult Question one step farther: what determines which genes are expressed in any particular cell?

There is more to a gene than just the DNA segment that is the code for a protein. There are also DNA segments that are information for when and where that gene should be used to produce protein. These DNA segments that regulate the use of genes are called, not surprisingly, regulatory sequences, or sometimes, control elements. Every gene has one or more control elements; some genes have many control elements, allowing them to have very complex patterns of regulation.

Control elements, by themselves, do little. To function, they must have specific proteins bound to them. We might think of control elements as a kind of "parking spaces" on the DNA, where different types of proteins can park. When one of these specific types of proteins has parked on the DNA, it signals to the cellular machinery that the nearby gene is to be used. Thus, what makes a cell become a particular type of cell is the gene-control proteins that it contains. These proteins control which genes are used in that cell. Our question now becomes: What determines the production of these gene-control proteins?

To answer this question, we need to discuss some embryology. A fertilized egg is not exactly homogeneous. Rather, it contains a variety of chemicals, some of which are proteins, whose amounts vary within the egg. This is illustrated in the figure below, in which each color

represents a different chemical. This asymmetric distribution of chemicals enables the egg to have a definite "top" and "bottom," "head" and "tail," and "left" and "right," even before any obvious embryological development has occurred.

When the fertilized egg starts to develop, it first divides into two cells, then these divide to form four cells, then these divide to form 8 cells, and so on. For a "generic" vertebrate embryo, we see something like that shown in the figure below. On the right-hand side of the

top row, we see the stage called the blastula, which is a hollow ball of cells. In cross section, colored to match the figure above, this hollow ball would look somewhat as shown here:

Cells on the top contain different molecules than cells on the bottom. Similarly, cells on either side contain different molecules. This gives the embryo a top, bottom, head, tail, left, and right.

The molecules we have illustrated here in different colors control gene expression. They can be either gene-control proteins, or chemicals that activate gene-control proteins. As a result of the uneven distribution of these proteins, each cell in the embryo acquires its own combination of these proteins, in specific concentrations. The result is that cells in different parts of the embryo "turn on," or begin to use, different genes.

As cells begin to use different genes, they begin to do different things. Among the things they do is move. The first set of movements, called gastrulation, brings cells from different parts of the embryo into contact. The contact between cells acts as a signal to activate new sets of genes, which causes new cell movements. Through the repeated sequence of cell movements, cell contact, and gene activation, the business of embryo development is controlled--and the numbers of different kinds of cells increases.

The morphology of the embryo, and of the animal that finally is formed, is established by this series of cell movements and changes in gene expression. The overall controls are the proteins that are responsible for communication between cells, the gene-control proteins, and the cellular information-relay system that enables cell-cell communication to change the patterns of gene activation. This basic description applies to all of the developing portions of the embryo.

An important feature of this kind of embryo developmental control system is that it works on a very small scale. When the embryo is only 2 cells, or 4 cells, or 8 cells, then the entire embryo can communicate. As the embryo grows larger, however, and as the number of cells increases, then the control systems function only on small portions of the embryo. As the eye begins to form, these kinds of gene-control systems operate within the "field" of eye-forming cells. As the ear begins to form, these kinds of gene-control systems operate within the "field" of ear-forming cells. As the liver begins to form, or as the pancreas begins to form, there are similar kinds of controls.

One organ-development system for which a great deal is known (but not yet everything) is the limb. We will discuss it as an example, recognizing that other organ systems undoubtedly develop through similar kinds of genetic control mechanisms.

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Last updated: 31 December 2005
Comments: Jose Bonner, OSO
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