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Fig. 7. A scheme summarizing the possible functions of Notch1 in maintaining the
multipotency of retinal progenitor cells and in photoreceptor cell
differentiation. During normal retinal development (A), Notch1 is
expressed in RPCs (blue) and is required for the expression of Hes1 and Hes5,
which function to repress proneural gene expression and thus to inhibit cell
differentiation. Release from Notch1 inhibition occurs gradually, in only a
few cells at a time, and these cells will differentiate into the different
retinal cell types (G, ganglion; C, cone; A, amacrine; H, horizontal; BPL,
bipolar; MG, Mueller glia). Inactivation of Notch1 in the RPCs during
early stages of retinogenesis does not result in premature differentiation
into the different early cell types (B). The premature loss of Notch1
activity resulted in differentiation of most RPCs into cone-photoreceptor
precursors expressing Otx2, Crx and the early cone marker Thrß2. These
cone precursors differentiate to mature cones during postnatal stages, thus
following the normal temporal order of the differentiation of
photoreceptors.
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