Biology Reference
In-Depth Information
TABLE 20.1
Key Ramogens in Branching Organs: the Species is Mouse Unless
Specified Otherwise. Original Sources for the Data can be Found in
Michael and Davies
53
Main paracrine
ramogen
Branching system
Tracheae in
D. melanogaster
Branchless
(FGF homologue)
via Breathless
(FGFR homologue)
Lung
FGF10 via FGFRIIIb
Pancreas
FGF10 via FGFRIIIb
Mammary gland
FGF7 via FGFRIIIb
Kidney
GDNF via GFR
a
1-Ret
complex
Prostate
FGF 7 via FGFRIIIb
signalling molecules inhibits branching in lungs
42,43
and kidneys.
9
Interactions with the
matrix are also required, as they are in the MDCK cell system. Laminins and nidogen
are needed for branching in salivary glands
44
e
46
and kidneys,
47,48
while the branching
epithelia of lungs and mammary glands fail to develop properly in animals in which collagen
synthesis is inhibited.
49,50
Proteolysis by the matrix is also required, either to clear a passage
for the advancing epithelium or to effect more subtle biochemical changes in the matrix.
51
Unfortunately, the precise cellular mechanisms that allow multicellular epithelial tubes to
sprout new tips are still far from clear. Vertebrate epithelial cells tend to proliferate as branch-
ing takes place, but while proliferation does tend to be localized to the growing tips,
52
there is
no evidence that mitoses are orientated to push cells out in any particular direction here
(though oriented mitoses may be used to achieve later elongation of branches once they
have formed
d
see Chapters 22 and 23). The ultrastructure of the epithelium is somewhat
relaxed at the tips, at least in salivary glands
54,55
and kidneys,
56
suggesting that cells there
are specialized for rearrangement and possibly also for direct locomotion. There is little
evidence for the construction of a motile leading edge analogous to those seen in MDCK cells
and insect tracheae but, at least in kidney it is possible to detect fine matrix-rich processes
that reach out from the basal side of the tips of the epithelium,
38
and which become very
long and obvious when the growth of the tips has been frustrated by depriving them of
glycosaminoglycans.
57
It is tempting to speculate that these are filopodia and that the
growing front of the epithelium shows 'classical' motile character, although at this stage
such a conjecture is merely speculation. It is supported, though, by the observation that
low concentrations of cytochalasin D, which seem to disrupt cell-cell adhesion at the tip
even more than usually, cause tip cells to scatter into the surrounding mesenchyme.
58
Also
in the kidney, the apical surfaces of cells at the tip are particularly rich in actin filaments
58
(
Figure 20.9
) that may drive the sprouting of a new epithelial tip through cell wedging
(Chapter 18).
