RBFOX3/NeuN is dispensable for visual function

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控因子，参与神经环路平衡、神经发生与突触形成过程。Rbfox3在神经元中广泛表达，但在视网膜中，其表达仅局限于神经节细胞层以及内核层的部分细胞。Rbfox3在视网膜中呈层特异性表达模式，这提示其存在功能性作用，但目前RBFOX3在视网膜中的具体功能仍不明确。Rbfox3纯合敲除（Rbfox3-/-）小鼠表现出视觉学习能力缺陷，因此阐明RBFOX3在视网膜中的功能，对解读相关行为学实验结果至关重要。本研究发现，Rbfox3在视网膜中的表达受发育进程调控，并特异性表达于视网膜的神经节细胞、无长突细胞与水平细胞中。研究证实，Rbfox3的缺失会导致视网膜内网状层——即突触形成的关键区域——厚度降低。Rbfox3缺失后，神经节细胞与无长突细胞的数量并无异常。Rbfox3-/-小鼠的视网膜神经节细胞向其靶脑区的神经投射也保持正常。尤为重要的是，Rbfox3-/-小鼠的非成像与成像视觉功能均处于正常水平。综上，本研究结果表明，RBFOX3对于视觉功能并非必需。