Nerve growth factor is expressed by postmitotic avian retinal horizontal cells and supports their survival during development in an autocrine mode of action.
Cell death in the developing retina is regulated, but so far little is known about what factors regulate the cell death. Several neurotrophic factors and receptors, including the neurotrophins and Trk receptors, are expressed during the critical time. We have studied the developing avian retina with respect to the role of nerve growth factor (NGF) in these processes. Our starting point for the work was that NGF and its receptor TrkA are expressed in a partially overlapping pattern in the inner nuclear layer of the developing retina. Our results show that TrkA and NGF-expressing cells are postmitotic. The first NGF-expressing cells were found on the vitreal side of the central region of E5.5-E6 retina. This pattern changed and NGF-expressing cells identified as horizontal cells were later confined to the external inner nuclear layer. We show that these horizontal cells co-express TrkA and NGF, unlike a subpopulation of amacrine cells that only expresses TrkA. In contrast to the horizontal cells, which survive, the majority of the TrkA-expressing amacrine cells die during a period of cell death in the inner nuclear layer. Intraocular injections of NGF protein rescued the dying amacrine cells and injection of antisense oligonucleotides for NGF that block its synthesis, caused death among the TrkA-expressing horizontal cells, which normally would survive. Our results suggest that NGF supports the survival of TrkA expressing avian horizontal cells in an autocrine mode of action in the retina of E10-E12 chicks. The cells co-express TrkA and NGF and the role for NGF is to maintain the TrkA-expressing horizontal cells. The TrkA-expressing amacrine cells are not supported by NGF and subsequently die. In addition to the effect on survival, our results suggest that NGF plays a role in horizontal cell plasticity.
Karlsson
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Department of Neuroscience, Unit of Developmental Neuroscience, Biomedical Center, Uppsala University, S-751 23 Uppsala, Sweden.
Mayordomo
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Reichardt
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Catsicas
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Hallböök
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D000818:Animals; D019898:Autocrine Communication; D001973:Bromodeoxyuridine / Q000378:metabolism; D016923:Cell Death / Q000235:genetics; D002454:Cell Differentiation; D002455:Cell Division; D002470:Cell Survival / Q000187:drug effects; D002642:Chick Embryo; D018507:Gene Expression Regulation, Developmental; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D020287:In Situ Nick-End Labeling; D008845:Microinjections; D020932:Nerve Growth Factor / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D016376:Oligonucleotides, Antisense / Q000494:pharmacology; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D020917:Receptor, trkA / Q000235:genetics / Q000378:metabolism; D012160:Retina / Q000166:cytology / Q000196:embryology* / Q000378:metabolism*
D016376:Oligonucleotides, Antisense; D012333:RNA, Messenger; D020932:Nerve Growth Factor; D020917:Receptor, trkA; D001973:Bromodeoxyuridine