The role of Meis genes is lens and retina development

Abstract

SummaryWhile significant insights into the functional role of some transcription factors for eye formation have been accomplished, much less is known about the intricate wiring of the gene regulatory network (GRN) that controls the earliest stages of eye development. Here we focus on the role of Meis homeobox genes in mammalian lens and retina development. It is well established that Pax6 represents a key node in the GRN governing lens induction. Meis1 and Meis2 were proposed to be essential upstream regulators of Pax6 during lens morphogenesis. This hypothesis is corroborated by the fact that Meis1/Meis2 double‐deficient mice phenocopy Pax6 mutant mice at the lens placode stage. We demonstrate that Meis1 and Meis2 homeoproteins regulate Pax6 gene via two redundant (shadow) enhancers, EE and SIMO. Simultaneous genetic ablation of EE and SIMO enhancers demostrates their requirement for lens induction. Using conditional gene targeting in mice at optic cup stage we provide evidence of a role of Meis genes in the process of retina development. Combined, our data indicate that Meis1 and Meis2 genes are required for normal lens and retina development.