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Fig. 7. A model of the specification, organization and maintenance of vertebrate
retinal cells. (A) Retinal cell type specification occurs prior to the OV
stage. By the OV stage depicted here, retinal cells are already biased to
become either RPE or neuroretinal cells, as shown by the striped green and
yellow region. (B) When the surface ectoderm comes in close contact with the
OV, FGF1 and/or FGF2 from the surface ectoderm signals through Chx10 to
organize the NR, adjacent to the future lens. Chx10 then represses the
expression of Mitf (directly or indirectly) to maintain neuroretinal
cell identity, perhaps through the regulation of Fgf8, Fgf9 and/or
Fgf15 and other neuroretinal genes. Cells that are distant from the
surface ectoderm, and thus from FGF1 and/or FGF2, do not express Chx10,
allowing Mitf expression to continue, thus organizing the RPE at the
back of the developing eye. The RPE, by contrast, appears to be organized by
activin signals from the posterior ocular mesenchyme
(Fuhrmann et al., 2000),
signals that may act through Mitf and other genes essential for RPE
formation, such as Otx1, Otx2
(Martinez-Morales et al.,
2001), Pax2 and Pax6
(Baumer et al., 2003). Mitf
appears to maintain RPE cell identity by the activation of downstream genes,
such as pigmentation enzyme-encoding genes. Finally, although the mechanism is
unknown, Mitf may also negatively regulate Chx10 to maintain RPE cell
identity.
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