INDUCTION OF CELL-GROWTH BY INSULIN AND INSULIN-LIKE GROWTH-FACTOR-I IS ASSOCIATED WITH JUN EXPRESSION IN THE OTIC VESICLE

The present report investigates the cellular mechanisms involved in th e regulation of cell proliferation by insulin and insulin-like growth factor-I (IGF-I) in the developing inner ear. The results show that in sulin and IGF-I stimulate cell proliferation in the otic vesicle. This effect is associated with the induction of the expression of the nucl ear proto-oncogene c-jun. The temporal profile of Jun expression coinc ided with the proliferative period of growth of the otic vesicle. IGF- I promoted the hydrolysis of a membrane glycosyl-phosphatidylinositol, which was characterised as the endogenous precursor for inositol phos phoglycan (IPG). Both purified IPG and a synthetic analogue, -alpha-D- glucopyranosyl)-D-myo-inositol-1,2-cyclic phosphate (C3), were able to mimic the effects of IGF-I on Jun expression. Anti-IPG antibodies blo cked the effects of IGF-I, which were rescued by the addition of IPG o r its analogue. These results suggest that the sequence involving the hydrolysis of membrane glycolipids and the expression of c-jun and c-f os proto-oncogenes is part of the mechanism that activates cell divisi on in response to insulin and IGF-I during early organogenesis of the avian inner ear. The implications of these observations for otic devel opment and regeneration are briefly discussed. J. Comp. Neurol. 398:32 3-332, 1997. (C) 1998 Wiley-Liss, Inc.