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Vsx2 Controls Eye Organogenesis and Retinal Progenitor Identity Via Homeodomain and Non-Homeodomain Residues Required for High Affinity DNA Binding

Figure 10

Regulation of pigmentation programs in wild-type and mutant RPCs.

(A) During early eye development, Mitf is expressed in optic neuroepithelial cells (MitfONC) in response to upstream activators. Vsx2 expression is activated in the newly specified retinal domain by upstream activators, which leads to repression of Mitf in RPCs (MitfRPC) and suppression of the pigmentation program. (B) In orJ mice, Mitf persists in RPCs because the VSX2 protein is absent, which increases the probability that pigmentation will occur. (C) In R200Q mice, VSX2[R200Q] protein is present but unable to bind DNA, allowing Mitf to persist in RPCs, increasing the probability of pigmentation. (D) In R227W mice, VSX2[R227W] protein is present and may still suppress the pathway that leads to pigmentation in orJ and R200Q RPCs, but its interaction with Mitf combined with its weak DNA binding activity engages a novel positive feedback loop that activates a robust pigmentation program. Our genetic data place Otx1 downstream of p27 and D-Mitf, but the mechanism causing its elevated expression is not clear.

Figure 10

doi: https://doi.org/10.1371/journal.pgen.1002924.g010