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

STEM CELLS AND Renewal IN EPITHELIAL TISSUES
1225
ON VILLUS
IN CRYPT,
UNDER
INFLUENCE
OF WNT
NOTCH
ACTIVATED
absorptive cells
LATERAL
INHIBITION
transit amplifying cells
secretory cell
DELTA
EXPRESSED
Figure 22–9 How Notch signaling, in
combination with Wnt, maintains stem
cells and drives cell diversification
in the intestine. Wnt signaling leads to
expression of Notch and Delta in the cells
of the crypt, and Delta-Notch signaling
in the crypt mediates lateral inhibition
between adjacent cells. Cells expressing
higher levels of Delta eventually activate
Notch in their neighbors, adopt a secretory
fate, and stop dividing; their neighbors,
with activated Notch, are prevented
from differentiating and keep on dividing.
Essentially the same process operates
at the crypt base, where the Paneth cells
express higher levels of Delta to prevent
stem cells from differentiating, and in
the transit amplifying population, where
nascent secretory cells express higher
levels of Delta. Division continues in the
Notch-activated cells as they move up the
crypt, until they escape from the influence
of Wnt and emerge onto the villi to become
absorptive cells.
NOTCH
ACTIVATED
stem cell
Paneth cell
DELTA
EXPRESSED
to be generated but no goblet cells are produced. This reflects the lateral inhibition
mechanism operating in normal animals: the nascent goblet (and other
secretory) cells express the Notch ligand
MBoC6
Delta
23.24/22.09
and thereby activate Notch in their
neighbors, inhibiting them from differentiating as secretory (Figure 22–9).
Delta-Notch signaling is crucial not only in the transit amplifying population,
but also at the crypt base: the Paneth cells express Delta and this activates Notch
in the stem cells, inhibiting differentiation. Without this influence, the stem cells
lose their special character and differentiate as secretory cells. Thus maintenance
of the intestinal stem-cell state requires a combination of signals, with both Wnt
and Notch acting as central players.
The Epidermal Stem-Cell System Maintains a Self-Renewing
Waterproof Barrier
Stem-cell systems are organized in many different ways, but they share some
underlying principles. Consider the epidermis, for example—the outer, epithelial
covering of the body. The epidermis undergoes continual renewal, but, unlike the
lining of the gut, it is multilayered or stratified. Stem cells are located in the basal
layer, and their progeny move outward toward the exposed surface, differentiating
as they go. They end up as lifeless scales or squames, which are eventually shed
from the surface of the skin (Figure 22–10). Even though the architecture of this
tissue is very different from that of the intestine, many of the same basic principles
apply. The stem cells depend for their existence on signals from a specific niche,
in this case the basal lamina and underlying connective tissue. The daughters of
stem cells that are committed to differentiation undergo several divisions as transit
amplifying cells (while still in the basal layer) before differentiating. Finally, a
stochastic independent-choice mechanism dictates the fates of the daughters of a
stem-cell division, allowing for increase in the number of stem cells when needed
for growth or wound healing. Most of the same signaling pathways that organize
the intestinal stem-cell system are also involved in regulating the epidermal stemcell
system, although with different individual roles.