原神经转录因子无调性碱性螺旋-环-螺旋转录因子 7 (ATOH7) 在发育中的神经视网膜的早期祖细胞中表达。在脊椎动物中，这对于视网膜神经节细胞（RGC）的发育至关重要，因为突变动物几乎完全没有 RGC、视神经发育不全以及视网膜血管发育异常。人类突变很罕见，会导致常染色体隐性视神经发育不全（ONH）或严重的血管变化，诊断为常染色体隐性遗传性原发性玻璃体持续性增生（PHPVAR）。为了更好地了解 ATOH7 在神经视网膜发育中的作用，我们创建了 ATOH7 敲除和表达 eGFP ATOH7 报告基因的人诱导多能干细胞 (hiPSC)，这些细胞分化为早期视网膜类器官。 ATOH7 调控的靶位点通过核酸酶切割和测序（CUT

The proneural transcription factor atonal basic helix-loop-helix transcription factor 7 (ATOH7) is expressed in early progenitors in the developing neuroretina. In vertebrates, this is crucial for the development of retinal ganglion cells (RGCs), as mutant animals show an almost complete absence of RGCs, underdeveloped optic nerves, and aberrations in retinal vessel development. Human mutations are rare and result in autosomal recessive optic nerve hypoplasia (ONH) or severe vascular changes, diagnosed as autosomal recessive persistent hyperplasia of the primary vitreous (PHPVAR). To better understand the role of ATOH7 in neuroretinal development, we created ATOH7 knockout and eGFP-expressing ATOH7 reporter human induced pluripotent stem cells (hiPSCs), which were differentiated into early-stage retinal organoids. Target loci regulated by ATOH7 were identified by Cleavage Under Targets and Release Using Nuclease with sequencing (CUT&RUN-seq) and differential expression by RNA sequencing (RNA-seq) of wildtype and mutant organoid-derived reporter cells. Additionally, single-cell RNA sequencing (scRNA-seq) was performed on whole organoids to identify cell type-specific genes. Mutant organoids displayed substantial deficiency in axon sprouting, reduction in RGCs, and an increase in other cell types. We identified 469 differentially expressed target genes, with an overrepresentation of genes belonging to axon development/guidance and Notch signaling. Taken together, we consolidate the function of human ATOH7 in guiding progenitor competence by inducing RGC-specific genes while inhibiting other cell fates. Furthermore, we highlight candidate genes responsible for ATOH7-associated optic nerve and retinovascular anomalies, which sheds light to potential future therapy targets for related disorders.