Nel positively regulates the genesis of retinal ganglion cells by promoting their differentiation and survival during development |
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Authors: | Chizu Nakamoto Soh-Leh Kuan Amy S Findlay Elaine Durward Zhufeng Ouyang Ewa D Zakrzewska Takuma Endo Masaru Nakamoto |
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Institution: | California Institute of Technology;aAberdeen Developmental Biology Group, School of Medical Sciences, University of Aberdeen, Aberdeen AB25 2ZD, United Kingdom;bDepartment of Neurosciences, Lerner Research Institute, Cleveland Clinic Foundation, and Department of Molecular Medicine, Cleveland Clinic Lerner College of Medicine, Case Western Reserve University, Cleveland, OH 44195 |
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Abstract: | For correct functioning of the nervous system, the appropriate number and complement of neuronal cell types must be produced during development. However, the molecular mechanisms that regulate the production of individual classes of neurons are poorly understood. In this study, we investigate the function of the thrombospondin-1–like glycoprotein, Nel (neural epidermal growth factor EGF]-like), in the generation of retinal ganglion cells (RGCs) in chicks. During eye development, Nel is strongly expressed in the presumptive retinal pigment epithelium and RGCs. Nel overexpression in the developing retina by in ovo electroporation increases the number of RGCs, whereas the number of displaced amacrine cells decreases. Conversely, knockdown of Nel expression by transposon-mediated introduction of RNA interference constructs results in decrease in RGC number and increase in the number of displaced amacrine cells. Modifications of Nel expression levels do not appear to affect proliferation of retinal progenitor cells, but they significantly alter the progression rate of RGC differentiation from the central retina to the periphery. Furthermore, Nel protects RGCs from apoptosis during retinal development. These results indicate that Nel positively regulates RGC production by promoting their differentiation and survival during development. |
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