Neuron
Volume 93, Issue 5, 8 March 2017, Pages 1110-1125.e5
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Article
SoxC Transcription Factors Promote Contralateral Retinal Ganglion Cell Differentiation and Axon Guidance in the Mouse Visual System

https://doi.org/10.1016/j.neuron.2017.01.029Get rights and content
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Highlights

  • SoxC transcription factors are highly expressed in contralateral RGCs

  • SoxC factors promote contralateral RGC differentiation via Notch signaling

  • SoxC factors regulate contralateral RGC axon outgrowth on chiasm cells

  • SoxC factors influence Nr-CAM and Plexin-A1 expression

Summary

Transcription factors control cell identity by regulating diverse developmental steps such as differentiation and axon guidance. The mammalian binocular visual circuit is comprised of projections of retinal ganglion cells (RGCs) to ipsilateral and contralateral targets in the brain. A transcriptional code for ipsilateral RGC identity has been identified, but less is known about the transcriptional regulation of contralateral RGC development. Here we demonstrate that SoxC genes (Sox4, 11, and 12) act on the progenitor-to-postmitotic transition to implement contralateral, but not ipsilateral, RGC differentiation, by binding to Hes5 and thus repressing Notch signaling. When SoxC genes are deleted in postmitotic RGCs, contralateral RGC axons grow poorly on chiasm cells in vitro and project ipsilaterally at the chiasm midline in vivo, and Plexin-A1 and Nr-CAM expression in RGCs is downregulated. These data implicate SoxC transcription factors in the regulation of contralateral RGC differentiation and axon guidance.

Keywords

retinal axon decussation
axon guidance
transcription factor
Notch1
Hes5
Plexin-A1
Nr-CAM

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