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

MECHANISMS OF patterN FORMatION
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Notch
Delta
(A)
(B)
cell
specialization
cell
specialization
each cell tends to
inhibit its neighbor
Delta
Notch
competition—
one cell wins
active
Notch
cell
specialization
cell
specialization
cell with active Delta specializes
and inhibits its neighbor from
doing likewise
inactive
Notch
are asymmetrically localized inside the dividing cells have this role in sensory
bristle development. They are also important in other contexts, as we now discuss.
Figure 21–35 Lateral inhibition. (A) The
basic mechanism of Notch-mediated
competitive lateral inhibition, illustrated for
just two interacting cells. In this diagram,
the absence of color on proteins or
effector lines indicates inactivity. (B) The
outcome of the same process operating
in a larger patch of cells. At first, all cells in
the patch are equivalent, expressing both
the transmembrane receptor Notch and
its transmembrane ligand Delta. Each cell
has a tendency to specialize (as a sensory
mother cell), and each sends an inhibitory
signal to its neighbors to discourage them
from also specializing in that way. This
creates a competitive situation. As soon
as an individual cell gains any advantage in
the competition, that advantage becomes
magnified. The winning cell, as it becomes
more strongly committed to differentiating
as a sensory mother cell, also inhibits its
neighbors more strongly. Conversely, as
these neighbors lose their capacity to
differentiate as sensory mothers, they also
lose their capacity to inhibit other cells from
doing so. Lateral inhibition thus makes
adjacent cells follow different fates.
Although the interaction is thought to be
normally dependent on cell–cell contacts,
the future sensory mother cell may be able
to deliver an inhibitory signal to cells that
are more than one cell diameter away—for
example, by sending out long protrusions
to touch them.
Asymmetric Cell Divisions Make Sister Cells Different
MBoC6 m22.60/22.35
Cell diversification does not always have to depend on extracellular signals: in
some cases, sister cells are born different as a result of an asymmetric cell division,
during which some significant set of molecules is divided unequally between
them. This asymmetrically segregated molecule (or set of molecules) then acts as
a determinant for one of the cell fates by directly or indirectly altering the pattern
of gene expression within the daughter cell that receives it (see Figure 21–12). We
have already encountered the asymmetric segregation of molecules in the context
of the early frog embryo: VegT RNA is localized in the vegetal region of the fertilized
egg. Following cell division, only vegetal daughter cells will inherit VegT RNA.
Asymmetric divisions often occur at the beginning of development, but they
are also encountered at some later stages. As mentioned for the sensory bristle,
they can set the scene for an exchange of Notch signals between the daughter
cells, with the signaling occurring after the cells have become separate and reinforcing
the differences between them. In the central nervous system, asymmetric
divisions have a key role in generating the very large numbers of neurons and
glial cells that are needed. A special class of cells becomes committed as neural
precursors, but instead of differentiating directly as neurons or glial cells, these
undergo a long series of asymmetric divisions through which a succession of
additional neurons and glial cells are added to the population. The process is best
understood in Drosophila, although there are many hints that something similar
occurs also in vertebrate neurogenesis.
In the embryonic central nervous system of Drosophila, the nerve-cell precursors,
or neuroblasts, are initially singled out from the neurogenic ectoderm
by a typical lateral-inhibition mechanism that depends on Notch. Each neuroblast
then divides repeatedly in an asymmetric fashion (Figure 21–36). At each
division, one daughter remains as a neuroblast, while the other, which is much