Critical role of TrkB and brain-derived neurotrophic factor in the differentiation and survival of retinal pigment epithelium.
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.
Liu
Z Z
ZZ
Department of Neurology, University of Chicago, Chicago, Illinois 60637, USA.
Zhu
L Q
LQ
Eide
F F
FF
D000221:Adaptation, Ocular / Q000502:physiology; D000818:Animals; D000906:Antibodies / Q000494:pharmacology; D001667:Binding, Competitive / Q000276:immunology; D019208:Brain-Derived Neurotrophic Factor / Q000235:genetics* / Q000276:immunology; D002454:Cell Differentiation / Q000502:physiology; D002470:Cell Survival / Q000502:physiology; D003623:Dark Adaptation / Q000502:physiology; D005123:Eye / Q000196:embryology; D018507:Gene Expression Regulation, Developmental / Q000502:physiology; D008565:Membrane Proteins / Q000235:genetics; D016296:Mutagenesis / Q000502:physiology; D010641:Phenotype; D010857:Pigment Epithelium of Eye / Q000737:chemistry* / Q000166:cytology* / Q000196:embryology; D012333:RNA, Messenger / Q000032:analysis; D020794:Receptor Protein-Tyrosine Kinases / Q000235:genetics*; D020801:Receptor, Ciliary Neurotrophic Factor; D011956:Receptors, Cell Surface / Q000235:genetics; D017475:Receptors, Nerve Growth Factor / Q000235:genetics*; D051880:Receptors, Notch; D014982:Xenopus laevis
D000906:Antibodies; D019208:Brain-Derived Neurotrophic Factor; D008565:Membrane Proteins; D012333:RNA, Messenger; D020801:Receptor, Ciliary Neurotrophic Factor; D011956:Receptors, Cell Surface; D017475:Receptors, Nerve Growth Factor; D051880:Receptors, Notch; D020794:Receptor Protein-Tyrosine Kinases