Molecular Biology of the Cell by Bruce Alberts, Alexander Johnson, Julian Lewis, David Morgan, Martin Raff, Keith Roberts, Peter Walter by by Bruce Alberts, Alexander Johnson, Julian Lewis, David Morg

1186 Chapter 21: Development of Multicellular Organisms
motile
germ cell
unpolarized
state
source of CXCL12
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.
bleb at
leading edge
(A) NO CXCL12 – BASIC MOTILITY
(B) CXCL12 GRADIENT –
GUIDED MOTILITY
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 MBoC6 cells when n22.222/22.45 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.