Biology Reference
In-Depth Information
FIGURE 20.5
The different types of tubule structure seen in different zones of one body segment's tracheal
system in
D. melanogaster
.
The powerful genetics of
D. melanogaster
has allowed identification of specific mechanisms
to confine motility to the branch tips, either instead of, or in addition to, modulation of
motility by cell geometry. Tip cells show very much higher levels of MAP-kinase activation
than do cells in the 'shafts' behind the tips.
21,22
This restriction of activation depends on
a mechanism of lateral inhibition in which tip cells inhibit the sensitivity of their neighbours
to Branchless, the extracellular activator of MAP-kinase during tracheal branching. There are
at least two mechanisms for this lateral inhibition. One relies on Notch-Delta signalling. Delta
is expressed in the tip cells as a consequence of MAP-kinase activation by Branchless. Delta is
a ligand for the protein Notch, and activates the Notch pathway in neighbouring cells. Notch
has several effects in the cells that express it; it down-regulates Delta and it down-regulates
the expression of Breathless, the receptor for Branchless.
21
The net effect is that neighbours of
Delta-expressing tip cells are inhibited from being induced, by Branchless, to become tip cells
themselves (
Figure 20.6
).
When the first edition of this topic was written, it was thought that there was a second
system of lateral inhibition based on diffusion of Sprouty, an inhibitor of MAP-kinase
produced especially strongly by tip cells but also somewhat by the non-tip cells.
26,27
In the
intervening years, Sprouty has been extensively studied and it is no longer thought to be
a diffusible molecule capable of setting up lateral inhibition. Instead, it is now seen as an
intracellular (rather than diffusible) inhibitor of FGF-type activation of the MAP-kinase
pathway that keeps sensitivity to FGF signalling within safe limits.
27
In the absence of
Sprouty, even cells back from the tip, which receive lower concentrations of Branchless
