Fig. 3.

Model by which Foxn4 promotes the amacrine and horizontal cell fates but suppresses the alternative photoreceptor and ganglion cell fates in early retinal progenitor cells (RPCs). a Schematic illustration of retinal phenotype in Foxn4 null mutant mice. b Early RPCs are capable of generating ganglion, amacrine, horizontal, and photoreceptor cells. c Foxn4 specifies early RPCs into amacrine and horizontal cells by activating the expression of Ptf1a, Neurod1, and Neurod4, three bHLH transcription factors (TFs) involved in the specification of these two cell types. Meanwhile, Foxn4 may simultaneously suppress the ganglion fate also by activating the expression of these three bHLH factors due to their activity to repress the expression of Atoh7 and Pou4f2. Another possibility is that Foxn4 may directly repress Atoh7 and Pou4f2 expression. Foxn4 suppresses photoreceptor fates by directly activating Dll4-Notch signaling which in turn represses the expression of Otx2, Crx, TRβ2, and perhaps other TFs involved in photoreceptor fate determination and differentiation