Another important survival signal for many types of migratory cells, including primordial germ cells, blood cell precursors, and neural-crest-derived pigment cells, depends on a receptor tyrosine kinase called Kit. This is expressed on the surface of the migrant cells, and a protein ligand, called Steel factor, is produced by the cells of the tissue through which the cells migrate and/or in which they come to settle. Individuals with mutations in the genes for either of these proteins have deficits in pigmentation, blood cells, and germ cells (Figure 21–47).
changing patterns of cell adhesion Molecules Force cells Into New arrangements
Patterns of gene expression govern embryonic cell movements in many ways. They regulate cell motility, cell shape, and the production of proteins that guide migration. Importantly, they also determine the sets of adhesion molecules that the cells display on their surface. Through changes in its surface molecules, a cell can break old attachments and make new ones. Cells in one region may develop surface properties that make them cohere with one another and become segregated from a neighboring group of cells with different surface chemistry.
Experiments done half a century ago on early amphibian embryos showed that the effects of selective cell–cell adhesion can be so powerful that they can bring about an approximate reconstruction of the normal structure of an early postgastrulation embryo after the cells have been artificially dissociated and mixed up. When these cells are reaggregated into a random mixture, the cells spontaneously sort themselves out according to their original germ-layer origins (Figure 21–48). As discussed in Chapter 19, cadherin proteins have a central role in the sorting process (see Figure 19–9). Cadherins belong to a large and varied family of Ca2+-dependent cell–cell adhesion proteins, and they and other cell–cell adhesion proteins are differentially expressed in the various tissues of the early embryo. Antibodies against these proteins interfere with the normal selective adhesion between cells of a similar type.
Changes in the patterns of expression of the various cadherins correlate closely with the changing patterns of association among cells during various developmental processes, including gastrulation, neural tube formation, and somite formation. These cell rearrangements are likely to be regulated and driven in part by
Figure 21–48 Sorting out by adhesion. cells from different parts of an early amphibian embryo will sort out according to their origins. In the classical experiment shown here, mesoderm cells (green), neural plate cells (blue), and epidermal cells (red) have been disaggregated and then reaggregated in a random mixture. they sort out into an arrangement reminiscent of a normal embryo, with a “neural tube” internally, epidermis externally, and mesoderm in between. (Modified from p.L. townes and J. holtfreter, J. Exp. Zool. 128:53– 120, 1955. With permission from Wiley-Liss.) the cadherin pattern. In particular, cadherins appear to have a major role in controlling the formation and dissolution of epithelial sheets and clusters of cells (see Movie 19.1). They not only glue one cell to another but also provide anchorage for intracellular actin filaments at the sites of cell–cell adhesion. In this way, the pattern of stresses and movements in the developing tissue is regulated according to the pattern of cell adhesions.