Kuwajima Takaaki, Soares Célia A, Sitko Austen A, Lefebvre Véronique, Mason Carol
Department of Pathology and Cell Biology, College of Physicians and Surgeons, Columbia University, New York, NY 10032, USA.
Department of Pathology and Cell Biology, College of Physicians and Surgeons, Columbia University, New York, NY 10032, USA.
Neuron. 2017 Mar 8;93(5):1110-1125.e5. doi: 10.1016/j.neuron.2017.01.029. Epub 2017 Feb 16.
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.
转录因子通过调控诸如分化和轴突导向等多种发育步骤来控制细胞特性。哺乳动物的双眼视觉回路由视网膜神经节细胞（RGCs）向大脑同侧和对侧靶点的投射组成。同侧RGC特性的转录编码已被确定，但对侧RGC发育的转录调控了解较少。在这里，我们证明SoxC基因（Sox4、11和12）通过与Hes5结合从而抑制Notch信号传导，作用于祖细胞到有丝分裂后转变过程，以实现对侧而非同侧RGC的分化。当有丝分裂后RGCs中的SoxC基因缺失时，对侧RGC轴突在体外视交叉细胞上生长不良，并且在体内视交叉中线处向同侧投射，RGCs中Plexin - A1和Nr - CAM的表达下调。这些数据表明SoxC转录因子参与对侧RGC分化和轴突导向的调控。
