title: Nel positively regulates the genesis of retinal ganglion cells by promoting their differentiation and survival during development.
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.
authors.affiliation: Aberdeen Developmental Biology Group, School of Medical Sciences, University of Aberdeen, Aberdeen AB25 2ZD, United Kingdom Department 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.
authors.forename: Chizu
authors.initials: C
authors.lastname: Nakamoto
authors.forename: Soh-Leh
authors.initials: SL
authors.lastname: Kuan
authors.forename: Amy S
authors.initials: AS
authors.lastname: Findlay
authors.forename: Elaine
authors.initials: E
authors.lastname: Durward
authors.forename: Zhufeng
authors.initials: Z
authors.lastname: Ouyang
authors.forename: Ewa D
authors.initials: ED
authors.lastname: Zakrzewska
authors.forename: Takuma
authors.initials: T
authors.lastname: Endo
authors.forename: Masaru
authors.initials: M
authors.lastname: Nakamoto
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000235:genetics; D030161:Avian Proteins / Q000235:genetics*; D002454:Cell Differentiation / Q000235:genetics*; D002470:Cell Survival / Q000235:genetics; D002645:Chickens; D018507:Gene Expression Regulation, Developmental; D006023:Glycoproteins / Q000235:genetics*; D012160:Retina / Q000254:growth & development* / Q000378:metabolism; D012165:Retinal Ganglion Cells; D013234:Stem Cells / Q000166:cytology / Q000378:metabolism; D019699:Thrombospondins / Q000235:genetics / Q000378:metabolism*
chemical_list: D030161:Avian Proteins; D006023:Glycoproteins; D019699:Thrombospondins