Figure 9. Models of rax function.

(A) Analysis of the rax mutant indicates that rax function is not necessary for activation of key EFTFs pax6, otx2, lhx2, or six3. rax expression is necessary for the correct expression of other key eye genes mab21l2, foxn4, myc, myb, vsx1, in addition to other factors. Dotted orange lines indicate putative, early interactions within the eye field gene regulatory network not supported by these analyses, although later, indirect effects of rax inactivation does affect their expression. Solid grey lines indicate previously described interactions not addressed in this work, but consistent with our data, and solid black lines indicate interactions supported by these analyses. (B) A key forebrain patterning event necessary for correct retina formation is the activation of a repressor(s) by rax, whose role is to down-regulate fezf2 and hesx1 in the anterior neural plate, creating a hole within their expression domains starting by late gastrula stages (St. 13). As shown in (C), when this repression of fezf2 and hesx1 fails to occur we propose that they contribute to establishment of non-retinal diencephalic (blue arrows) and telencephalic (red arrows) properties within presumptive retinal tissue, resulting in the expansion of these forebrain identities into the retinal region. Fate map in (C) adapted with permission from (Eagleson and Harris, 1990).