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. 2013 Sep 20;8(9):e76489. doi: 10.1371/journal.pone.0076489

Figure 7. Scheme depicting Pax6 roles during the transition from proliferating retinal progenitor to differentiating retinal neuron.

Figure 7

(A) In normal cycling retinal progenitors, Pax6 regulates the balance between proliferation promoting (i.e. Nr2e1, Vsx2, Hedgehog (HH) signaling) and inhibiting factors (i.e. Plagl1). These in turn regulate the expression of genes which induce either progression of (i.e. Ccnd1–3) or withdrawal (P27 Kip1, P57 Kip2) from the cell cycle. It is also required for the expression of bHLH proneural factors (Neurog2, Atoh7, and Ascl1) presumed to inhibit cell-cycle factors as well as promote specific retinal lineages. (B) Pax6 loss from RPCs results in aberrant cell-cycle exit as Ccnd1–3, as well as P27 Kip1 and P57 Kip2, are elevated and several cell-fate determination factors show reduced (bHLH proneural factors) or increased (Six3, Sox2) expression. The combined outcome of these alterations is delayed differentiation of the Pax6-deficient cells to only one subclass of retinal interneurons.