INSULIN AND INSULIN-LIKE GROWTH-FACTOR SYSTEM COMPONENTS GENE-EXPRESSION IN THE CHICKEN RETINA FROM EARLY NEUROGENESIS UNTIL LATE DEVELOPMENT AND THEIR EFFECT ON NEUROEPITHELIAL CELLS

To better understand the role of insulin-related growth factors in neu ral development, we have characterized by in situ hybridization in chi cken embryonic retina the patterns of gene expression for insulin, ins ulin-like growth factor I (IGF-I), their respective receptors and the IGF binding protein 5 (IGFBP5) from early stages (E6) until late stage s (E18)-an analysis not performed yet in any species. In addition, we studied the effect of insulin and IGF-I on cultured neuroepithelial ce lls. Insulin receptor mRNA and IGF-I receptor mRNA were both present a nd showed a similar, widespread pattern throughout retina development Insulin mRNA could be detected only by reverse transcription coupled t o polymerase chain reaction. IGF-I mRNA was concentrated in the ciliar y processes and extraocular muscles early in development (embryonic da y 6; E6) and in maturing retinal ganglion cells subsequently (E9-15). IGFBP5 mRNA was preferentially localized in the more differentiated ce ntral retinal zone and was maximally concentrated in the inner nuclear and ganglion cell layers at E9. These findings suggest a near constit utive expression of insulin receptor and IGF-I receptor genes, while I GF-I and IGFBP5 showed a highly focal spatiotemporal regulation of gen e expression. Insulin and IGF-I, already at 10(-8) M, increased the pr oportion of PM1-positive neuroepithelial cells found in E5 retinal cul tures without affecting significantly the total number of proliferatin g cells. Together, these data support the finding that, during early n eurogenesis in chicken retina, insulin and IGF-I have a specific parac rine/autocrine action. This action, as well as possible effects elicit ed subsequently, may be dictated by restricted local synthesis of the ligands and limited access to the factors contained in the Vitreous hu mour. In the case of IGF's role, local IGFBPs expression can contribut e to the fine modulation.