Ruiz Department of Ophthalmology and Visual Science, McGovern Medical School at The University of Texas Health Science Center at Houston (UTHealth), Houston, TX 77030, USA.
Department of Ophthalmology, Baylor College of Medicine, Houston, TX 77030, USA.
Cell Rep. 2019 Apr 16;27(3):900-915.e5. doi: 10.1016/j.celrep.2019.03.077.
In the mouse retina, more than 30 retinal ganglion cell (RGC) subtypes have been classified based on a combined metric of morphological and functional characteristics. RGCs arise from a common pool of retinal progenitor cells during embryonic stages and differentiate into mature subtypes in adult retinas. However, the cellular and molecular mechanisms controlling formation and maturation of such remarkable cellular diversity remain unknown. Here, we demonstrate that T-box transcription factor T-brain 1 (Tbr1) is expressed in two groups of morphologically and functionally distinct RGCs: the orientation-selective J-RGCs and a group of OFF-sustained RGCs with symmetrical dendritic arbors. When Tbr1 is genetically ablated during retinal development, these two RGC groups cannot develop. Ectopically expressing Tbr1 in M4 ipRGCs during development alters dendritic branching and density but not the inner plexiform layer stratification level. Our data indicate that Tbr1 plays critical roles in regulating the formation and dendritic morphogenesis of specific RGC types.
在小鼠视网膜中，已经根据形态和功能特征的综合指标对超过 30 种视网膜神经节细胞（RGC）亚型进行了分类。RGC 是在胚胎发育阶段从视网膜祖细胞的共同池中产生的，并在成年视网膜中分化为成熟的亚型。然而，控制这种显著细胞多样性形成和成熟的细胞和分子机制尚不清楚。在这里，我们证明 T 盒转录因子 T 脑 1（Tbr1）在两种形态和功能上明显不同的 RGC 中表达：方位选择 J-RGC 和一组具有对称树突分支的 OFF 持续 RGC。当在视网膜发育过程中遗传敲除 Tbr1 时，这两种 RGC 群无法发育。在发育过程中，将 Tbr1 异位表达在 M4 ipRGC 中会改变树突分支和密度，但不会改变内丛状层分层水平。我们的数据表明，Tbr1 在调节特定 RGC 类型的形成和树突形态发生中发挥关键作用。
