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 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.
León
Y
Y
Instituto de Investigaciones Biomédicas, Consejo Superior de Investigaciones Científicas, Madrid, Spain.
Sanz
C
C
Giráldez
F
F
Varela-Nieto
I
I
D000818:Animals; D015152:Blotting, Northern; D015153:Blotting, Western; D002455:Cell Division / Q000187:drug effects; D002642:Chick Embryo; D004247:DNA / Q000096:biosynthesis / Q000235:genetics; D007758:Ear, Inner / Q000166:cytology / Q000187:drug effects / Q000254:growth & development*; D007004:Hypoglycemic Agents / Q000494:pharmacology*; D017403:In Situ Hybridization; D007295:Inositol Phosphates / Q000494:pharmacology; D007328:Insulin / Q000494:pharmacology*; D007329:Insulin Antagonists / Q000494:pharmacology; D007334:Insulin-Like Growth Factor I / Q000494:pharmacology*; D016759:Oncogene Protein p65(gag-jun) / Q000096:biosynthesis* / Q000235:genetics; D009924:Organ Culture Techniques; D011134:Polysaccharides / Q000494:pharmacology; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology; D013045:Species Specificity
D007004:Hypoglycemic Agents; D007295:Inositol Phosphates; D007328:Insulin; D007329:Insulin Antagonists; D016759:Oncogene Protein p65(gag-jun); D011134:Polysaccharides; C028039:inositol phosphate glycan; D007334:Insulin-Like Growth Factor I; D004247:DNA