Meis homeobox genes control cell competence within the eye-specified neuroepithelium (ChIP-seq)

Vertebrate eye is derived from the neuroepithelium, surface ectoderm, and extracellular mesenchyme. Eye-specified neuroepithelium forms the optic cup in which spatial separation of three domains is established, namely, the region of multipotent retinal progenitor cells (RPCs), the ciliary margin zone (CMZ) possessing both neurogenic and non-neurogenic potential, and the optic disc (OD), the interface between the optic stalk and the neuroretina. Here, we show by genetic ablation in the developing optic cup that Meis1 and Meis2 homeobox genes function redundantly to maintain the retinal progenitor pool while they simultaneously suppress the expression of genes characteristic of CMZ and OD fates. Furthermore, we demonstrate that Meis transcription factors bind the regulatory regions of RPC-, CMZ-, and OD-specific genes, thus providing a mechanistic insight into the Meis-dependent gene regulatory network. Our work uncovers the essential role of Meis1 and Meis2 as regulators of cell fate competence and guardians of spatial territories in the vertebrate eye.