Purchase this article with an account.
DD Hunter, T Claudepierre, C Verioti, RE Burgeson, M Koch, WJ Brunken; Expression and Function of Beta-Netrin in the Retina and Optic Nerve . Invest. Ophthalmol. Vis. Sci. 2002;43(13):2705.
Download citation file:
© ARVO (1962-2015); The Authors (2016-present)
Purpose: Components of the extracellular matrix (ECM), including the netrins, are implicated in neural development. RNA encoding one netrin, ß-netrin (Koch et al., 2000) is expressed at high levels in retina. Here, we examined the expression of ß-netrin and a potential receptor (DCC) in the retina and optic nerve, and investigated the function of ß-netrin. Methods: ß-netrin and DCC immunohistochemistry and ß-netrin in situ hybridization were performed on frozen sections of developing and mature mouse retinae. Antibodies against ß-netrin and DCC were used for immunoprecipitations. Activity of ß-netrin was assessed in E15 retinal explants. Retinae from ß-netrin-null mice created by homologous recombination were analyzed histologically. DiI crystals were placed on retinal flat-mounts to analyze axon tracts. Results: In the adult retina, ß-netrin was expressed in the basement membranes of blood vessels, the optic nerve, the neural retina and the retinal pigmented epithelium (RPE). It was also expressed on the apical surface of the retina and in the outer plexiform layer. In the adult, ß-netrin is produced in the RPE and glia. Early in development, ß-netrin is diffuse across the neural retina; upon Müller cell differentiation, it becomes restricted to the apex and base of Müller cell processes, and Müller cells produce ß-netrin in vitro. DCC, a netrin receptor, co-localizes with ß-netrin in embyronic and adult retina. ß-netrin and DCC co-immunoprecipitate, suggesting they form a complex. Antibodies to DCC enhance Müller cell proliferation in vitro. ß-netrin did not promote neurite outgrowth from E15 retinal explants. Retinae from ß-netrin-null mice are grossly normal; however, nuclear and plexiform layers are hyperplastic. Application of DiI to the vitreal surface labels ganglion cells axons and IPL dendrites; the fasciculation of processes in mutant retinae is lower than that of the controls. Conclusion: We demonstrate that one component of the retinal ECM, ß-netrin, may interact with DCC to inhibit cellular proliferation and to form a permissive molecular environment for neurite extension and fasciculation. These data support our hypothesis that ECM components are important regulators of retinal differentiation.
This PDF is available to Subscribers Only