Transcription factor Foxd1 is required for the specification of the temporal retina in mammals

Abstract

The organization of the visual system is different in birds and mammals. In both, retinal axons project topographically to the visual targetsinthebrain;but whereasinbirdsvisualfibersfrom the entireretina decussateatthe opticchiasm,inmammals,anumberofaxons from the temporal retina diverge at the midline to project ipsilaterally. Gain-of-function experiments in chick raised the hypothesis that the transcription factor Foxd1 specifies retinal temporal identity. However, it remains unknown whether Foxd1 is necessary for this function. In mammals, the crucial role of Foxd1 in the patterning of the optic chiasm region has complicated the interpretation of its cell-autonomous function in the retina. Furthermore, target molecules identified for Foxd1 are different in chicks and mice, leading to question the function of Foxd1 in mammals. Here we show that in the mouse, Foxd1 imprints temporal features in the retina such as axonal ipsilaterality and rostral targeting incollicular areas and that EphA6is a Foxd1 downstream effector that sends temporal axons to the rostral colliculus. In addition, our data support a model in which the desensitization of EphA6 by ephrinA5 in cis is not necessary for theproper functioningofEphA6. Overall, these results indicate thatFoxd1functionsasaconserved determinantoftemporal identity but reveal that the downstream effectors, and likely their mechanisms of action, are different in mammals and birds. © 2011 the authors.