The role of miR-124a in early development of the Xenopus eye.

It has been reported that miR-124a is abundant in the central nervous system including the eye, and is related to neurogenesis in several species. However, the role of miR-124a in the eye remains unclear. In this study, we show that the expression of miR-124a in Xenopus laevis begins along the neural fold, including the protruding eye anlagen, at a low level at around stage 18; its expression level gradually increases in the neural tube and the eye as embryos develop into later stages and then maintains at a high level in eye to adult stages. Microinjection of a miR-124a precursor at the 8-cell stage leads to malformation of the optic nerve and optic cup, indicating the importance of maintaining low levels of miR-124a during early embryonic development. In addition, miR-124a overexpression markedly down regulates the expression of its predicted targets Lhx2, Hairy2, Gli3, NeuroD1 and Otx2 in/around the eye anlagen, and the interaction of miR-124a with the 3' UTR of Lhx2 represses gene expression as shown by luciferase assays. Moreover, excess miR-124a inhibits cell proliferation in the eye of Xenopus embryos during retinogenesis. These results indicate that miR-124a acts as a post-transcriptional regulator in the genetic network controlling eye morphogenesis and neurogenesis. The mechanism of miR-124a's early interaction with the genetic network may also persist in its later role in the maturing and adult eye and brain.