Lin Yi-Sian, Kuo Kuan-Ting, Chen Shih-Kuo, Huang Hsien-Sung
Graduate Institute of Brain and Mind Sciences, College of Medicine, National Taiwan University, Taipei, Taiwan.
Department of Pathology, College of Medicine, National Taiwan University, Taipei, Taiwan.
PLoS One. 2018 Feb 5;13(2):e0192355. doi: 10.1371/journal.pone.0192355. eCollection 2018.
RBFOX3/NeuN is a neuronal splicing regulator involved in neural circuitry balance, as well as neurogenesis and synaptogenesis. Rbfox3 is expressed in neurons; however, in the retina, expression is restricted to cells in the ganglion cell layer and some cells of the inner nuclear layer. Rbfox3 is expressed in a layer-specific manner in the retina, which implies a functional role, however, the role of RBFOX3 in the retina is unknown. Rbfox3 homozygous knockout (Rbfox3-/-) mice exhibit deficits in visual learning; therefore, understanding the role of RBFOX3 in the retina is critical for interpreting behavioral results. We found Rbfox3 expression was developmentally regulated in the retina and specifically expressed in ganglion cells, amacrine cells and horizontal cells of the retina. We demonstrate deletion of Rbfox3 resulted in a reduction in the thickness of the inner plexiform layer of the retina, where synapses are formed. Number of ganglion cells and amacrine cells is normal with loss of Rbfox3. Innervation of retinal ganglion cells into their targeted brain regions is normal in Rbfox3-/- mice. Importantly, Rbfox3-/- mice displayed normal non-image and image forming functions. Taken together, our results suggest RBFOX3 is dispensable for visual function.
RBFOX3/NeuN是一种神经元剪接调节因子,参与神经回路平衡以及神经发生和突触形成。Rbfox3在神经元中表达;然而,在视网膜中,其表达仅限于神经节细胞层的细胞和内核层的一些细胞。Rbfox3在视网膜中以层特异性方式表达,这暗示了其功能作用,然而,RBFOX3在视网膜中的作用尚不清楚。Rbfox3纯合敲除(Rbfox3-/-)小鼠在视觉学习方面存在缺陷;因此,了解RBFOX3在视网膜中的作用对于解释行为结果至关重要。我们发现Rbfox3的表达在视网膜中受到发育调控,并特异性地表达于视网膜的神经节细胞、无长突细胞和水平细胞中。我们证明,Rbfox3的缺失导致视网膜内丛状层厚度减小,而内丛状层是形成突触的部位。Rbfox3缺失时,神经节细胞和无长突细胞的数量正常。Rbfox3-/-小鼠中,视网膜神经节细胞向其靶向脑区的神经支配正常。重要的是,Rbfox3-/-小鼠表现出正常的非成像和成像功能。综上所述,我们的结果表明RBFOX3对于视觉功能是可有可无的。