Biology Reference
In-Depth Information
FIGURE 19.7 Cleft palate in the human mouth. The sketch is taken from a viewpoint directly below the mouth,
with the lower jaw 'removed' for clarity. The nasal cavity and passages to it are shaded grey.
palate fusion has been studied in more detail than most epithelial fusions. Many of the
signals involved in the process have been identified, though there is still much to discover
at the level of morphogenetic mechanisms.
The inside of the oral cavity is covered by a multilayered epithelium that consists of
a columnar epithelium and an overlying periderm. When growth of the palatal shelves brings
the epithelia fromopposing shelves together at themidline, the columnar epitheliameet apical
domain to apical domain. The first event connected directly with the process of fusion is
a change in the behaviour of cells as the epithelia approach. Soon after the palatal shelves
elevate to grow across the top of the tongue, cells at their medial edges begin to produce large
numbers of microvilli 14 and then produce filopodia that project towards the oncoming oppo-
site shelf. 15 This presumably reflects activity of small GTPases such as cdc42, although this
assumption has not been investigated experimentally. Formation of the filopidia requires
the presence of the signalling molecule TGF
3 in the epithelium; filopidia do not form in
b
3 / embryos unless these animals are treated with exogenous TGF
tgf
3.
The filopodia are coated in a thick covering of proteoglycans, 16 particularly chondroitin
sulphate. 17 This glycosaminoglycan seems to be critical for the initial adhesion of converging
palate shelves, and if it is removed by chondroitinase enzymes or if its synthesis is blocked
with
b
b
-D-xylosides, adhesion fails. 18 The precise nature of the adhesive mechanisms is not
yet understood, but the use of chondroitin sulphate here and in neural tube closure (below)
suggests that one basic mechanism is being re-used in several places. Once adhesion has
been achieved, the periderm cells move away to the top and bottom of the medial edge, where
they die, 19,20 and the underlying columnar epithelia meet.
The line of adheringmedial epithelia, needed for protection of the underlying stroma before
fusion, are now an obstruction to the fusion of this stroma to make a continuous tissue and it
has to be removed. Two processes seem to be involved in this: removal by apoptosis and
removal by epithelial-to-mesenchymal transition and subsequent migration. 'TUNEL' stain-
ing of the fusing palate reveals a high frequency of apoptosis (see Chapter 24) in the epithelial
cells between apposed palatal shelves, but only once the shelves have met. 20 This apoptosis is
important to the process of fusion. Blocking apoptosis with inhibitors of caspases prevents
proper destruction of the medial epithelium and its associated basement membrane and,
b
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