Insulin-like growth factor-I stimulates neurogenesis in chick retina by regulating expression of the alpha 6 integrin subunit.
Insulin-like growth factor I (IGF-I) strongly stimulates the generation of differentiated neurons in cultures of neuroepithelial cells of the embryonic chick neural retina in the presence of a laminin-1 tissue culture substrate. Treatment of cultured neuroepithelial cells with IGF-I rapidly up-regulated the mRNA coding for the alpha 6 integrin subunit whereas specific reduction of alpha 6 subunit levels by treatment with an alpha 6 integrin antisense oligonucleotide resulted in reduced neuronal differentiation in vitro. Although IGF-I immunoreactivity is seen throughout the neural retina, expression of IGF-I mRNA is confined to the pigment epithelium during the period of neurogenesis in vivo. Neutralization of the endogenous IGF-I with a blocking antibody down-regulated levels of alpha 6 integrin mRNA and reduced the production of differentiated retinal neurons in vivo. These data indicate a role for IGF-I in the generation of retinal neurons mediated by the interaction of laminin with its alpha 6 integrin subunit-containing receptor.
Frade
J M
JM
Cajal Institute for Neurobiology, CSIC, Madrid, Spain.
Martí
E
E
Bovolenta
P
P
Rodríguez-Peña
M A
MA
Pérez-García
D
D
Rohrer
H
H
Edgar
D
D
Rodríguez-Tébar
A
A
D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology; D015703:Antigens, CD / Q000235:genetics*; D002454:Cell Differentiation; D002478:Cells, Cultured; D002642:Chick Embryo; D018507:Gene Expression Regulation, Developmental; D007334:Insulin-Like Growth Factor I / Q000502:physiology*; D039503:Integrin alpha6; D009474:Neurons / Q000166:cytology*; D009500:Neutralization Tests; D012160:Retina / Q000166:cytology / Q000196:embryology*
D000911:Antibodies, Monoclonal; D015703:Antigens, CD; D039503:Integrin alpha6; D007334:Insulin-Like Growth Factor I