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.
Instituto de Investigaciones Biomédicas, Consejo Superior de Investigaciones Científicas, Madrid, Spain.
Y
Y
León
C
C
Sanz
F
F
Giráldez
I
I
Varela-Nieto
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