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

MORPHOGENESIS
1187
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.)
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
MBoC6 m22.86/22.46
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 Ca 2+ -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.)