SoxC Transcription Factors Promote Contralateral Retinal Ganglion Cell Differentiation and Axon Guidance in the Mouse Visual System

• Published in: Neuron (Cambridge, Mass.) Vol. 93; no. 5; pp. 1110 - 1125.e5
• Main Authors: Kuwajima, Takaaki, Soares, Célia A., Sitko, Austen A., Lefebvre, Véronique, Mason, Carol
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 08.03.2017; Elsevier Limited
• Subjects: Animals; Axon guidance; Axon Guidance - physiology; Axons; Axons - metabolism; Binding sites; Binocular vision; Cell Differentiation - physiology; Ganglion cells; Gene regulation; Genes; Hes5; Ligands; Mammals; Mice, Transgenic; Nerve Tissue Proteins - metabolism; Neurogenesis; Notch protein; Notch1; Nr-CAM; Optic Chiasm - metabolism; Plexin-A1; Retina; Retina - cytology; Retina - metabolism; retinal axon decussation; Retinal ganglion cells; Retinal Ganglion Cells - cytology; Retinal Ganglion Cells - metabolism; Rodents; SOXC Transcription Factors - metabolism; transcription factor; Transcription factors; Visual aspects; Visual Pathways - metabolism; Visual perception; Visual system; transcription factor; Nr-CAM; Notch1; axon guidance; retinal axon decussation; Hes5; Plexin-A1
• ISSN: 0896-6273; 1097-4199
• DOI: 10.1016/j.neuron.2017.01.029

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. •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 Kuwajima et al. identify SoxC transcription factors in the differentiation and guidance of retinal ganglion cells that project contralaterally. The SoxC factors regulate Hes5 in the Notch pathway and expression of guidance receptors Plexin-A1 and Nr-CAM, respectively.