Retinoid-dependent gene expression regulates early morphological events in the development of the murine retina

Endogenous retinoids have been implicated in the axial patterning of the embryonic vertebrate retina; however, no studies have directly examined how asymmetric retinoid-dependent gene expression regulates early morphological events in the development of the retina. Here we used a line of indicator mice that possess a retinoid-dependent transgene to examine the relationship between retinoic acid (RA)-dependent gene expression and events occurring during early eye morphogenesis, such as the closure of the optic disc. We found that retinoid-regulated gene expression shifts along the dorsal/ventral axis of the embryonic retina; at embryonic day (E) E11.5 transgene expression is restricted to the neuroepithelium in dorsal retina, and by E14.5 only immature cells located in ventral retina and the dorsal retinal margins demonstrate transgene activation. By manipulating RA levels, we were not only able to systemically alter RA-dependent gene expression along the dorsal/ventral axis, but also to affect retinal morphology. In particular, reducing RA availability resulted in the abnormal closure of the optic fissure. These results indicate that asymmetric levels of RA regulate early RA-dependent gene expression in the eye and demonstrate that the normal pattern of retinoid-dependent gene transcription along the dorsal/ventral axis is critical for the proper development of the vertebrate retina.