Meis homeobox genes control cell competence within the eye-specified neuroepithelium (RNA-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.脊椎动物眼睛起源于神经上皮（neuroepithelium）、表面外胚层（surface ectoderm）与细胞外间充质（extracellular mesenchyme）。经眼部特化的神经上皮会形成视杯，视杯内建立了三个空间分隔的结构域：分别为多能视网膜祖细胞（multipotent retinal progenitor cells, RPCs）区域、同时具备神经发生与非神经发生潜能的睫状缘区（ciliary margin zone, CMZ），以及连接视柄与神经视网膜的视盘（optic disc, OD）。本研究通过对发育中视杯进行基因敲除实验，证实同源盒基因Meis1与Meis2存在功能冗余，可维持视网膜祖细胞库的稳态，同时抑制睫状缘区与视盘细胞命运相关特征基因的表达。此外，本研究证实Meis转录因子可结合视网膜祖细胞、睫状缘区及视盘特异性基因的调控区域，从而为解析依赖Meis的基因调控网络提供了机制层面的见解。本研究揭示了Meis1与Meis2作为脊椎动物眼睛内细胞命运能力调控因子与空间区域守护者的核心功能。