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E.C. Tolhurst, F. Zaucke, D.O. Clegg; Thrombospondin–4 is Expressed in Embryonic Mouse Retina and Supports Integrin–Dependent Neurite Outgrowth . Invest. Ophthalmol. Vis. Sci. 2004;45(13):5348.
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© ARVO (1962-2015); The Authors (2016-present)
Purpose: Thrombospondin–4 (TSP–4) is a multidomain glycoprotein of the extracellular matrix whose function is largely unknown. Previous work has shown that TSP–4 is expressed in retina and supports neurite outgrowth from chick retinal cells in co–culture experiments (Arber and Caroni, 1995, J Cell Biol 131:1083–1094). The aim of our study was to determine when and where TSP–4 is expressed in developing retina and to identify the cellular receptor for TSP–4. Methods: TSP–4 localization in embryonic C57/BL6 mouse retina was determined by immunohistochemistry for multiple developmental time points. In vitro neurite outgrowth assays using explants of embryonic day 15 mouse retina were performed using purified TSP–4 as a substrate. Various function–blocking antibodies against integrin receptors were used to determine the integrin dependence of neurite extension and adhesion on TSP–4. Results: TSP–4 expression is widespread in the early embryonic mouse retina and becomes localized to the retinal ganglion cells and inner retina as development progresses. Retinal cells extending processes on TSP–4 were identified as retinal ganglion cells, and antibodies to the ß1 integrin subunit inhibited the neurite extension on TSP–4. Conclusions: Our findings indicate that TSP–4 is present in the embryonic mouse retina and is a permissive substrate for ß1 integrin–dependent process extension by retinal ganglion cells.
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