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Volume 17, Number 22, Issue of November 15, 1997 pp. 8749-8755
Critical Role of TrkB and Brain-Derived Neurotrophic Factor in the Differentiation and Survival of Retinal Pigment Epithelium
Received June 10, 1997; revised Aug. 18, 1997; accepted Aug. 28, 1997.
Zheng Z. Liu, Ling Q. Zhu, and Fernette F. Eide Department of Neurology, University of Chicago, Chicago, Illinois 60637
In the vertebrate eye, the retinal pigment epithelium (RPE) and the neural retina arise from a single layer of neuroectoderm. Factors influencing the differentiation of retinal neurons have been identified; however, little is known about molecules directing the differentiation of the RPE. Here we have found that the neurotrophin brain-derived neurotrophic factor (BDNF) plays an autocrine role in the differentiation and survival of Xenopus laevis RPE. Fluorescent in situ hybridization studies showed a precise co-expression of BDNF and its receptor trkB in the retinal neuroepithelium and actively differentiating RPE; in vitro studies demonstrated survival- and differentiation-promoting effects in serum-free explants and dissociated cultures. When a dominant negative mutant of the trkB receptor was expressed in developing embryos, severe arrest of RPE differentiation was seen with persistence of nestin- and Notch-positive neuroblasts.
Key words: BDNF; trkB; neurotrophin; retinal pigment epithelium; differentiation; retina; dominant negative
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