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

CELL–CELL JUNCTIONS
1041
(A)
(B)
50 µm
Figure 19–8 Changing patterns of
cadherin expression during construction
of the vertebrate nervous system. The
figure shows cross sections of the early
chick embryo, as the neural tube detaches
from the ectoderm and then as neural
crest cells detach from the neural tube.
(A, B) Immunofluorescence micrographs
showing the developing neural tube labeled
with antibodies against (A) E-cadherin (blue)
and (B) N-cadherin (yellow). (C) As the
patterns of gene expression change, the
different groups of cells segregate from one
another according to the cadherins they
express. (Micrographs courtesy of Miwako
Nomura and Masatoshi Takeichi.)
ectoderm
(C)
cells expressing E-cadherin
cells expressing cadherin 6B
cells expressing N-cadherin
cells expressing cadherin 7
neural tube
neural crest
cells
Cadherins play a crucial part in these cell-sorting processes during development.
The appearance and disappearance of specific cadherins correlate with
MBoC6 m19.12/19.08
steps in embryonic development where cells regroup and change their contacts
to create new tissue structures. In the vertebrate embryo, for example, changes in
cadherin expression are seen when the neural tube forms and pinches off from
the overlying ectoderm: neural tube cells lose E-cadherin and acquire other cadherins,
including N-cadherin, while the cells in the overlying ectoderm continue
to express E-cadherin (Figure 19–8A and B). Then, when the neural crest cells
migrate away from the neural tube, these cadherins become scarcely detectable,
and another cadherin (cadherin 7) appears that helps hold the migrating cells
together as loosely associated cell groups (Figure 19–8C). Finally, when the cells
aggregate to form a ganglion, they switch on expression of N-cadherin again. If
N-cadherin is artificially overexpressed in the emerging neural crest cells, the cells
fail to escape from the neural tube.
Studies with cultured cells further support the idea that the homophilic binding
of cadherins controls these processes of tissue segregation. In a line of cultured
fibroblasts called L cells, for example, cadherins are not expressed and the cells
do not adhere to one another. When these cells are transfected with DNA encoding
E-cadherin, E-cadherins on one cell bind to E-cadherins on another, resulting
in cell–cell adhesion. If L cells expressing different cadherins are mixed together,
they sort out and aggregate separately, indicating that different cadherins preferentially
bind to their own type (Figure 19–9A), mimicking what happens when
cells derived from tissues that express different cadherins are mixed together. A
similar segregation of cells occurs if L cells expressing different amounts of the
same cadherin are mixed together (Figure 19–9B). It therefore seems likely that
both qualitative and quantitative differences in the expression of cadherins have
a role in organizing tissues.
(A)
cell expressing
E-cadherin
cell expressing low
level of E-cadherin
(B)
SORTING
OUT
cell expressing
N-cadherin
cell expressing
high level of E-cadherin
SORTING
OUT
Figure 19–9 Cadherin-dependent cell
sorting. Cells in culture can sort themselves
out according to the type and level of
cadherins they express. This can be
visualized MBoC6 by labeling m19.13/19.09 different populations of
cells with dyes of different colors. (A) Cells
expressing N-cadherin sort out from cells
expressing E-cadherin. (B) Cells expressing
high levels of E-cadherin sort out from cells
expressing low levels of E-cadherin. The
cells expressing high levels adhere more
strongly and end up internally.