title: SoxC Transcription Factors Promote Contralateral Retinal Ganglion Cell Differentiation and Axon Guidance in the Mouse Visual System.
abstract: 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.
authors.affiliation: Department of Pathology and Cell Biology, College of Physicians and Surgeons, Columbia University, New York, NY 10032, USA. Electronic address: tk2288@columbia.edu.
authors.forename: Takaaki
authors.initials: T
authors.lastname: Kuwajima
authors.affiliation: Department of Pathology and Cell Biology, College of Physicians and Surgeons, Columbia University, New York, NY 10032, USA.
authors.forename: Célia A
authors.initials: CA
authors.lastname: Soares
authors.affiliation: Department of Neuroscience, College of Physicians and Surgeons, Columbia University, New York, NY 10032, USA.
authors.forename: Austen A
authors.initials: AA
authors.lastname: Sitko
authors.affiliation: Department of Cellular and Molecular Medicine, Orthopaedic and Rheumatologic Research Center, Cleveland Clinic Lerner Research Institute, Cleveland, OH 44195, USA.
authors.forename: Véronique
authors.initials: V
authors.lastname: Lefebvre
authors.affiliation: Department of Pathology and Cell Biology, College of Physicians and Surgeons, Columbia University, New York, NY 10032, USA; Department of Neuroscience, College of Physicians and Surgeons, Columbia University, New York, NY 10032, USA; Department of Ophthalmology, College of Physicians and Surgeons, Columbia University, New York, NY 10032, USA. Electronic address: cam4@columbia.edu.
authors.forename: Carol
authors.initials: C
authors.lastname: Mason
mesh_terms: D000818:Animals; D000071437:Axon Guidance / Q000502:physiology; D001369:Axons / Q000378:metabolism*; D002454:Cell Differentiation / Q000502:physiology*; D008822:Mice, Transgenic; D009419:Nerve Tissue Proteins / Q000378:metabolism; D009897:Optic Chiasm / Q000378:metabolism; D012160:Retina / Q000166:cytology / Q000378:metabolism*; D012165:Retinal Ganglion Cells / Q000166:cytology* / Q000378:metabolism*; D055751:SOXC Transcription Factors / Q000378:metabolism*; D014795:Visual Pathways / Q000378:metabolism*
chemical_list: D009419:Nerve Tissue Proteins; D055751:SOXC Transcription Factors
keywords: Hes5; Notch1; Nr-CAM; Plexin-A1; axon guidance; retinal axon decussation; transcription factor