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Receptor protein tyrosine phosphatases are expressed by cycling retinal progenitor cells and involved in neuronal development of mouse retina

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NEUROSCIENCE
卷 152, 期 3, 页码 618-645

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PERGAMON-ELSEVIER SCIENCE LTD
DOI: 10.1016/j.neuroscience.2008.01.016

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retinogenesis; proliferation; differentiation; adult retina

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Receptor protein tyrosine phosphatases (RPTPs) appear to coordinate many aspects of neural development, including cell proliferation, migration and differentiation. Here we investigated potential roles of RPTPs in the developing mouse retina. Using a degenerate oligonucleotide-based reverse transcription polymerase chain reaction approach, we identified 11 different RPTPs in the retina at embryonic stage 13 (E13). Subsequently, the expression patterns of RPTP kappa, RPTPJ, RPTPRR, RPTP sigma, RPTP epsilon and RPTP gamma in the retina from embryonic stages to adult were analyzed in detail using quantitative real-time-PCR, in situ hybridization, immunohistochemistry and Western blotting. At E13, all six RPTPs are expressed in actively cycling retinal progenitor cells and post-mitotic newborn retinal neurons. With ongoing maturation, RPTP kappa, RPTPJ, RPTPRR, RPTP sigma, RPTP epsilon and RPTP gamma display a different spatiotemporal regulation of mRNAs and proteins in the pre- and postnatal retina. Finally, in adulthood these six RPTPs localize to distinct cellular compartments of multiple retinal neurons. Additional studies in RPTP gamma(-/-) and RPTP beta/zeta(-/-) (also known as PTPRZ1, RPTP beta or RPTP zeta mice at postnatal stage 131 reveal no apparent differences in retinal laminar organization or in the expression pattern of specific retinal cell-type markers when compared with wild type. However, in RPTP beta/zeta(-/-) retinas, immunoreactivity of vimentin, a marker of Muller glial cells, is selectively reduced and the morphology of vimentin-immunoreactive radial processes of Muller cells is considerably disturbed. Our results suggest distinct roles of RPTPs in cell proliferation and establishing phenotypes of different retinal cells during retinogenesis as well as later in the maintenance of mature retina. (C) 2008 IBRO. Published by Elsevier Ltd. All rights reserved.

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