The transcription factor Tbx5 regulates direction-selective retinal ganglion cell development and image stabilization

转录因子Tbx5调控视网膜神经节细胞的方向选择性发育和图像稳定

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作者:Timour Al-Khindi ,Michael B Sherman ,Takashi Kodama ,Preethi Gopal ,Zhiwei Pan ,James K Kiraly ,Hao Zhang ,Loyal A Goff ,Sascha du Lac ,Alex L Kolodkin

Abstract

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.

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