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Fig. 10. A dual role for FGF10 in controlling mouse eyelid development. (A) In the
early phase of eyelid development, FGF10-FGFR2b signaling is required for cell
shape changes and proliferation of the prospective eyelid epithelium, leading
to coordinated growth of the eyelid anlagen. (B) In the late phase,
FGF10-FGFR2b signaling is involved in up-regulation of Tgfa and
activin ßB, and accumulation of F-actin in the epithelial leading edge
cells, thus directing epithelial cell migration, epithelial sheet movement,
and eyelid closure. The pathways indicated by the broken lines are suggested
by other studies (for review, see Xia and
Kao, 2004). It is not known whether FGF10 could directly regulate
the accumulation of F-actin or indirectly through TGF-
and/or activin
pathways. This study has shown that FGF10 is necessary for proper expression
of Shh in the basal layer of the eyelid tip epidermis
(Motoyama et al., 1998), and
for the integrity of the cell polarity of the eyelid basal epidermis.
FGF10-FGFR2b signaling orchestrates these genetic and cellular activities
during mouse eyelid fusion processes. These molecular interplays indeed result
from combinatorial regulation of FGF10 and other extrinsic and intrinsic
factors, which define the developmental context of developing eyelids. Other
ligands of FGFR2b must be required for growth of the eyelid anlagen, as
well.
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