Solomon H. Snyder Department of Neuroscience, The Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.
Solomon H. Snyder Department of Neuroscience, The Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA; Department of Otolaryngology & Head and Neck Surgery, The Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.
Curr Biol. 2022 Oct 10;32(19):4286-4298.e5. doi: 10.1016/j.cub.2022.07.064. Epub 2022 Aug 22.
The diversity of visual input processed by the mammalian visual system requires the generation of many distinct retinal ganglion cell (RGC) types, each tuned to a particular feature. The molecular code needed to generate this cell-type diversity is poorly understood. Here, we focus on the molecules needed to specify one type of retinal cell: the upward-preferring ON direction-selective ganglion cell (up-oDSGC) of the mouse visual system. Single-cell transcriptomic profiling of up- and down-oDSGCs shows that the transcription factor Tbx5 is selectively expressed in up-oDSGCs. The loss of Tbx5 in up-oDSGCs results in a selective defect in the formation of up-oDSGCs and a corresponding inability to detect vertical motion. A downstream effector of Tbx5, Sfrp1, is also critical for vertical motion detection but not up-oDSGC formation. These results advance our understanding of the molecular mechanisms that specify a rare retinal cell type and show how disrupting this specification leads to a corresponding defect in neural circuitry and behavior.
哺乳动物视觉系统处理的视觉输入多样性需要产生许多不同的视网膜神经节细胞 (RGC) 类型，每种类型都针对特定的特征进行了调整。产生这种细胞类型多样性所需的分子密码尚未得到很好的理解。在这里，我们专注于指定一种视网膜细胞类型所需的分子：小鼠视觉系统中向上优先的 ON 方向选择性神经节细胞 (up-oDSGC)。up-oDSGC 和 down-oDSGC 的单细胞转录组分析表明，转录因子 Tbx5 特异性表达于 up-oDSGC 中。up-oDSGC 中 Tbx5 的缺失导致 up-oDSGC 的形成出现选择性缺陷，以及相应的无法检测垂直运动的缺陷。Tbx5 的下游效应物 Sfrp1 对于垂直运动检测也很关键，但对于 up-oDSGC 的形成并非如此。这些结果推进了我们对指定罕见视网膜细胞类型的分子机制的理解，并表明破坏这种指定如何导致神经回路和行为的相应缺陷。
