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

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. •Up- and down-oDSGCs have distinct transcriptional profiles•Tbx5 is expressed by, and required for, the development of up-oDSGCs•Loss of Tbx5 in up-oDSGCs causes a selective defect in vertical image stabilization•Sfrp1, a Tbx5 downstream effector, is required for vertical image stabilization Little is known about the molecular code needed to specify different retinal ganglion cell types. Al-Khindi et al. show that the transcription factor Tbx5 is expressed by upward-preferring ON DSGCs and is required for their initial formation and the proper detection of vertical motion.