source of CXCL12 and various other white blood cells; of neurons in the developing brain; of myoblasts entering limb buds; of primordial germ cells as they travel toward the developing gonads; and of cancer cells when they metastasize.
Detailed studies of primordial-germ-cell migration have shown that CXCL12 signaling does not induce cell migration per se but rather serves to control its direction. In the absence of CXCL12 signaling, germ cells still display the membrane blebbing associated with cell migration, but the position of the cell front where blebs form is randomly chosen (Figure 21–46); if CXCL12 signaling is intact, blebbing is more frequent on the side of the cell that faces the source of CXCL12, resulting in directional migration.
the Distribution of Migrant cells Depends on Survival Factors
The final distribution of migrant cells depends not only on the routes they take, but also on whether they survive the journey and thrive in the environment they find at the journey’s end. Specific sites provide survival factors needed for specific types of migrant cells to survive.
Among the most important sets of migrant cells in the vertebrate embryo are those of the neural crest. They arise from the border region between the part of the ectoderm that will form epidermis and the part that will form the central nervous system. As the neural ectoderm rolls up to form the neural tube, the neural crest cells break loose from the epithelial sheet along this border region and set out on their long migrations (see Figure 19–8 and Movie 21.5). They settle ultimately in many sites and give rise to a surprising diversity of cell types. Some lodge in the skin and specialize as pigment cells; still others form skeletal tissue in the face. Still others will differentiate into the neurons and glial cells of the peripheral nervous system—not only in the sensory ganglia that lie close to the spinal cord, but also, following a much longer migration, in the wall of the gut.
The neural crest cells that give rise to the pigment cells of the skin and those that develop into the nerve cells of the gut depend on a secreted peptide called endothelin-3, which is produced by tissues along the migration pathways and acts as a survival factor for the migrating crest cells. In mutants with a defect in the gene for endothelin-3 or its receptor, many of these migrating crest cells die. As a result, the mutant individuals have nonpigmented (albino) patches of skin and a deficit of nerve cells in the intestine, especially its lower end, the large bowel, which becomes abnormally distended for lack of proper neural control—a potentially lethal condition called megacolon.
Figure 21–46 Directional migration by local blebbing. Germ cells migrate via protrusions that define the leading edge of the cell. the persistence and site of the protrusions are biased toward higher levels of cXcL12. thus, germ cells migrate up the cXcL12 gradient.
Figure 21–47 Effect of mutations in the Kit gene. Both the baby and the mouse are heterozygous for a loss-of-function mutation that leaves them with only half the normal quantity of Kit gene product. In  both cases, pigmentation is defective because pigment cells depend on the gene product as a receptor for a survival factor.  (courtesy of r.a. Fleischman, from r.a. Fleischman et al., Proc. Natl Acad. Sci. USA 88:10885–10889, 1991.)