Brodie-Kommit Justin, Clark Brian S, Shi Qing, Shiau Fion, Kim Dong Won, Langel Jennifer, Sheely Catherine, Ruzycki Philip A, Fries Michel, Javed Awais, Cayouette Michel, Schmidt Tiffany, Badea Tudor, Glaser Tom, Zhao Haiqing, Singer Joshua, Blackshaw Seth, Hattar Samer
Department of Biology, Johns Hopkins University, Baltimore, MD, USA.
John F. Hardesty, MD, Department of Ophthalmology and Visual Sciences, Washington University School of Medicine, St. Louis, MO, USA.
Sci Adv. 2021 Mar 12;7(11). doi: 10.1126/sciadv.abe4983. Print 2021 Mar.
Retinal ganglion cells (RGCs) relay visual information from the eye to the brain. RGCs are the first cell type generated during retinal neurogenesis. Loss of function of the transcription factor , expressed in multipotent early neurogenic retinal progenitors leads to a selective and essentially complete loss of RGCs. Therefore, is considered essential for conferring competence on progenitors to generate RGCs. Despite the importance of Atoh7 in RGC specification, we find that inhibiting apoptosis in deficient mice by loss of function of only modestly reduces RGC numbers. Single-cell RNA sequencing of -deficient retinas shows that RGC differentiation is delayed but that the gene expression profile of RGC precursors is grossly normal. -deficient RGCs eventually mature, fire action potentials, and incorporate into retinal circuitry but exhibit severe axonal guidance defects. This study reveals an essential role for in RGC survival and demonstrates -dependent and independent mechanisms for RGC specification.
视网膜神经节细胞(RGCs)将视觉信息从眼睛传递到大脑。RGCs是视网膜神经发生过程中产生的第一种细胞类型。在多能早期神经源性视网膜祖细胞中表达的转录因子功能丧失会导致RGCs选择性且基本完全丧失。因此, 被认为对于赋予祖细胞产生RGCs的能力至关重要。尽管Atoh7在RGCs特化中很重要,但我们发现通过 功能丧失来抑制缺陷小鼠中的细胞凋亡仅适度减少了RGCs的数量。对 -缺陷视网膜的单细胞RNA测序表明,RGCs分化延迟,但RGC前体细胞的基因表达谱基本正常。 -缺陷的RGCs最终成熟,产生动作电位,并融入视网膜回路,但表现出严重的轴突导向缺陷。这项研究揭示了 在RGCs存活中的重要作用,并证明了RGCs特化的 -依赖和独立机制。