Fig. 8. A model for directed differentiation of retinal progenitors towards horizontal and amacrine fates by the Foxn4-Ptf1a pathway. (A) Foxn4-expressing cells in the outer neuroblastic layer represent progenitors biased towards horizontal and amacrine fates (Li et al., 2004a). Subsets of Foxn4⁺ cells activate Ptf1a after exit from the cell cycle. Activation of Ptf1a depends on the Foxn4 function (Fig. 6). Ptf1a-expressing post-mitotic cells differentiate to horizontal or amacrine cells. (B) In the absence of Ptf1a, retinal precursors, which would normally activate Ptf1a, adopt ganglion cell fates or otherwise undergo apoptotic cell death (referred also in C). The cell fate switch to RGC takes place relatively quickly in the onbl after exit from the cell cycle. Green, horizontal cells; blue, amacrine cells; red, RGCs. Dark-red cells in B represent RGCs originating from Ptf1a-lineage-labeled precursor populations. (C) Foxn4 and Ptf1a control the genesis of amacrine and horizontal cells in cooperation with other retinogenic factors. Foxn4-expressing progenitors require sequential activation of Ptf1a and Prox1 for the genesis of horizontal cells. Foxn4 confers progenitors with the competence for the genesis of amacrine cells by activating the expression of Ptf1a, Math3 and Neurod1. Activation of Math3 or Neurod1 does not require Ptf1a function. The rod, cone, bipolar, ganglion and Müller cells are likely to be largely derived from the Pax6⁺ Foxn4^- progenitors via activation of other retinogenic factors, which are not shown here for simplicity. Abbreviations: GCL, ganglion cell layer; IPL, inner plexiform layer.