Laboratory of Transcriptional Regulation, Institute of Molecular Genetics of the Czech Academy of Sciences, 142 20 Prague 4, Czech Republic.
Laboratory of Genomics and Bioinformatics, Institute of Molecular Genetics of the Czech Academy of Sciences, 142 20 Prague 4, Czech Republic.
Proc Natl Acad Sci U S A. 2021 Mar 23;118(12). doi: 10.1073/pnas.2013136118.
The vertebrate eye is derived from the neuroepithelium, surface ectoderm, and extracellular mesenchyme. The neuroepithelium forms an optic cup in which the spatial separation of three domains is established, namely, the region of multipotent retinal progenitor cells (RPCs), the ciliary margin zone (CMZ)-which possesses both a neurogenic and nonneurogenic potential-and the optic disk (OD), the interface between the optic stalk and the neuroretina. Here, we show by genetic ablation in the developing optic cup that and 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 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 and as regulators of cell fate competence, which organize spatial territories in the vertebrate eye.
脊椎动物的眼睛来源于神经外胚层、表面外胚层和细胞外间质。神经外胚层形成一个视杯，其中建立了三个区域的空间分离，即多能视网膜祖细胞 (RPC) 的区域、具有神经发生和非神经发生潜力的睫状缘区 (CMZ) 以及视盘 (OD)，视柄和神经视网膜之间的界面。在这里，我们通过在发育中的视杯中的遗传消融表明， 和 同源盒基因在维持视网膜祖细胞池方面具有冗余功能，同时抑制 CMZ 和 OD 命运特征基因的表达。此外，我们证明 Meis 转录因子结合 RPC、CMZ 和 OD 特异性基因的调节区域，从而为 Meis 依赖的基因调控网络提供了机制上的见解。我们的工作揭示了 和 作为细胞命运能力的调节因子的重要作用，它们在脊椎动物眼睛中组织空间区域。
