Functional diversification and evolutionary origin of Otx family genes in the vertebrate retina

概要

Otx family homeobox transcription factors, Otx2 and Crx, are expressed in photoreceptor precursor cells and bind to the consensus DNA-binding sequence, but these two genes have distinct functions in retinal development. To examine functional redundancy of Otx2 and Crx, I analyzed knock-in mouse lines in which Crx is replaced by Otx2 and vice versa. I showed that Otx2 and Crx have nonexchangeable biological functions in photoreceptor development. Next, I analyzed the function of Otx2 in photoreceptor and bipolar cell development. High levels of Otx2 induce photoreceptor cell fate but not bipolar cell fate, whereas reduced Otx2 expression impairs bipolar cell maturation and survival. Moreover, I identified Otx2 and Crx in the lamprey genome using synteny analysis. It suggests that the last common ancestor of vertebrates possesses both Otx2 and Crx. I showed that expression pattern of Otx2 is different between lampreys and mice. These results suggest that neofunctionalization of Otx2 occurred in the jawed vertebrate lineage.