Biology Reference
In-Depth Information
FIGURE 20.6
The role of Notch and Delta in restriction of MAP-kinase activation to one tip cell in branching
tracheae of
D. melanogaster
.
because they do not reach forward with cytonemes, are responsive enough to sprout new
branches of their own, hence the name. Sprouty proteins are widespread phylogenetically
and the developing branching organs of mammals express several members of the family,
which act the same way to inhibit signalling from FGF and EGF receptor signals. In lungs,
for example, Sprouty2 is expressed in response to signalling by the primary ramogen,
FGF10, and it acts as an inhibitor of branching.
28
The branching epithelia of vertebrates (
Figure 20.7
) tend to be constructed on a larger scale
and the tips of branches are many cells wide even when they are actively advancing
(
Figure 20.8
: sprouting of single cells is, however, common in capillary endothelia). This
means that new sprouts are not led by motility of single cells and it also means that the activi-
ties of a group of cells have to be coordinated. Nevertheless, there is evidence that the same
set of control pathways may be used.
These epithelia ramify into mesenchymal cells that surround them, and their growth and
branching are controlled by a variety of paracrine signals that include FGF7 and FGF10 (both
of which signal via FGFRIIIB), EGF, TGF
a
and amphiregulin (all of which signal via RGFR),
HGF (which signals via Met) and GDNF (which signals via Ret/GFR
1, via
Met too).
29
Most organs use several of these ligands at once, although just one seems to play
a dominant role in each case (
Table 20.1
). Each receptor is capable of triggering both the MAP-
kinase and PI-3-kinase pathways
30
e
34
and experiments, in which these pathways are
inhibited by specific drugs, suggest that these pathways play similar roles to those described
a
1 and, via GFR
a
