Induction of cell growth by insulin and insulin-like growth factor-I is associated with Jun expression in the otic...

The present report investigates the cellular mechanisms involved in the regulation of cell proliferation by insulin and insulin-like growth factor-I (IGF-I) in the developing inner ear. The results show that insulin and IGF-I stimulate cell proliferation in the otic vesicle. This effect is associated with the induction of the expression of the nuclear proto-oncogene c-jun. The temporal profile of Jun expression coincided 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 phosphoglycan (IPG). Both purified IPG and a synthetic analogue, 6-O-(2-amino-2-deoxy-alpha-D-glucopyranosyl)-D-myoinositol-1,2-cyclic phosphate (C3), were able to mimic the effects of IGF-I on Jun expression. Anti-IPG antibodies blocked the effects of IGF-I, which were rescued by the addition of IPG or its analogue. These results suggest that the sequence involving the hydrolysis of membrane glycolipids and the expression of c-jun and c-fos proto-oncogenes is part of the mechanism that activates cell division in response to insulin and IGF-I during early organogenesis of the avian inner ear. The implications of these observations for otic development and regeneration are briefly discussed.