Insulin-like growth factor-I stimulates neurogenesis in chick retina by regulating expression of the alpha 6 integrin...

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.