Animal development involves dramatic cell movements, including the guided migration of individual cells, the adhesion and repulsion of groups of cells, and the complex extension, branching, or rolling up of epithelial tissues. Migrant cells, such as those of the neural crest, break loose from their original neighbors and travel through the embryo to colonize new sites. Many migrant cells, including primordial germ cells, are guided by chemotaxis dependent on the receptor CXCR4 and its ligand CXCL12. In general, cells that have similar adhesion molecules on their surfaces cohere and tend to segregate from other cell groups with different surface properties. Selective cell–cell adhesion is often mediated by cadherins; repulsion is often driven by ephrin–Eph signaling. Within an epithelial sheet, cells can rearrange themselves to drive epithelial convergence and extension, as in gastrulation. Many movements are coordinated through a Wnt-dependent planar-polarity signaling pathway that is also responsible for orienting cells correctly in various types of epithelium. Elaborate branched tubular structures, such as the airways of the lung, are generated through bidirectional signaling between an epithelial bud and the mesenchyme that it invades, in a process called branching morphogenesis. Epithelial tubes and vesicles can originate in various ways, most simply by the rolling up and pinching off of a segment of epithelium, as in the formation of the neural tube.
One of the most fundamental aspects of animal development is one we know surprisingly little about—how the size of an animal or an organ is determined. Why, for example, do we grow to be so much larger than a mouse? Even within a species, size can vary greatly; a Great Dane, for instance, can weigh over 40 times more than a Chihuahua (Figure 21–57).
Three variables define the size of an organ or organism: the number of cells, the size of the cells, and the quantity of extracellular material per cell. Size differences can arise from changes in any of these factors (Figure 21–58). If we compare a mouse with a human, for example, we find that the difference lies chiefly in the number of cells, there being roughly 3000 times more cells in a human, corresponding to a body that is roughly 3000 times more massive. Wild and cultivated species of food plants, on the other hand, often differ in body size chiefly because of differences of cell size.
The challenge, therefore, is to understand how cell numbers, cell size, and extracellular matrix production are regulated. First of all, we need to identify the signals that drive or inhibit growth. Then we need to discover how the signals themselves are regulated. In many cases, the size of an organ or of the body as a whole seems to be controlled homeostatically, so that the correct size is reached and maintained even in the face of drastic disturbances. This suggests that the developing structure somehow senses its own size and uses this information to regulate the signals for its own growth or shrinkage. In most cases, the nature of this feedback control remains a profound mystery.
In other cases, the duration of growth and the final size seem to be dictated by intracellular programs that take no cognizance of the size the structure has attained. These intracellular programs, too, present many mysteries, as we saw in our discussion of developmental timing. Very often, it seems, the sizes and proportions of body parts must depend on combinations of size-measuring feedback controls and intracellular programs, as well as on environmental influences such as nutrition.
The variation in control strategies is nicely illustrated by some classic transplantation experiments. If several fetal thymus glands are transplanted into a developing mouse, each grows to its characteristic adult size. In contrast, if multiple fetal spleens are transplanted, each ends up smaller than normal, but collectively they grow to the size of one adult spleen. Thus, thymus growth is regulated by local mechanisms intrinsic to the individual organ, whereas spleen growth is controlled by a feedback mechanism that senses the quantity of spleen tissue in the body as a whole. In neither case is the mechanism known.