Biology Reference
In-Depth Information
these labelled cells turn up in the mesenchyme and have an apparently completely mesen-
chymal phenotype.
17
This process of differentiation is again dependent on signalling by
TGF
3by
apoptosis or by mesenchyme-to-epithelium transition depends on the stage of the cell cycle
that they have reached, with only cells in G1 or S phases being able to undergo mesenchyme-
to-epithelium transition.
23
The pathway by which TGF
3: experiments with cultured cells suggest that whether cells respond to TGF
b
b
3 induces a mesenchymal phenotype
is somewhat complicated: it drives the production of the transcription factor Snail, and the
transcription factor LEF-1, which cooperates with
b
-catenin. Both of these activate transcrip-
tion of mesenchyme-type genes and inhibit the production of epithelium-type genes, partic-
ularly E-cadherin. The pathway also uses the PI-3-kinase pathway to inhibit GSK3
b
b
,which
would otherwise degrade
-
catenin and hold much of it at the membrane, unavailable for nuclear signalling, but with
falling E-cadherin,
b
-catenin and Snail. In epithelial cells, E-cadherin can 'mop up'
b
-catenin signalling rises, driving E-cadherin production down further
and so on in strong positive feedback.
23,24
Epithelial fusion is a necessary step in the formation of a tube by orthogonal invagination
(Chapter 18), as the folds at the crests of an invaginating trough have to fuse in order to
produce a tube from it (
Figure 19.9
). Proper fusion of the ectoderm is critical for closure of
the neural tube and for its separation from the dorsal surface of the embryo; failure of the
process leads to spina bifida (when in the trunk) or anencephaly (when in the head). Studies
in mice have identified well over 200 gene mutations that are associated with failure of neural
tube closure. Most, however, affect early processes such as invagination itself that set the
system up, and the events of fusion itself are still not well understood.
25
In neural tube closure, an epithelial sheet that began by including two ectodermal-
to-neurectodermal borders ends up without either. The closure must therefore involve
two sheet fusions
d
flanking epihelium to flanking epihelium and neurepihelium to neure-
pihelium
d
followedbythepartingoftheoldborders(
Figure 19.10
). Parting cannot happen
earlier than connection without risking the mechanical integrity of the whole embryo, but in
principle either fusion could happen first. Careful observation of mice reveals that different
levels of the anteroposterior axis show a different order: over the forebrain, flanking epithe-
lium and neurepithelium cells meet their opposite numbers at the same time, while over the
midbrain and hindbrain the flanking epitheliummakes contact first and neurepithelial cells
b
FIGURE 19.9
Fusion in the orthogonal invagination that forms the neural tube.
