Insulin-like growth factor 1 is required for survival of transit-amplifying neuroblasts and differentiation of otic neurons.
Neurons that connect mechanosensory hair cell receptors to the central nervous system derive from the otic vesicle from where otic neuroblasts delaminate and form the cochleovestibular ganglion (CVG). Local signals interact to promote this process, which is autonomous and intrinsic to the otic vesicle. We have studied the expression and activity of insulin-like growth factor-1 (IGF-1) during the formation of the chick CVG, focusing attention on its role in neurogenesis. IGF-1 and its receptor (IGFR) were detected at the mRNA and protein levels in the otic epithelium and the CVG. The function of IGF-1 was explored in explants of otic vesicle by assessing the formation of the CVG in the presence of anti-IGF-1 antibodies or the receptor competitive antagonist JB1. Interference with IGF-1 activity inhibited CVG formation in growth factor-free media, revealing that endogenous IGF-1 activity is essential for ganglion generation. Analysis of cell proliferation cell death, and expression of the early neuronal antigens Tuj-1, Islet-1/2, and G4 indicated that IGF-1 was required for survival, proliferation, and differentiation of an actively expanding population of otic neuroblasts. IGF-1 blockade, however, did not affect NeuroD within the otic epithelium. Experiments carried out on isolated CVG showed that exogenous IGF-1 induced cell proliferation, neurite outgrowth, and G4 expression. These effects of IGF-1 were blocked by JB1. These findings suggest that IGF-1 is essential for neurogenesis by allowing the expansion of a transit-amplifying neuroblast population and its differentiation into postmitotic neurons. IGF-1 is one of the signals underlying autonomous development of the otic vesicle.
Camarero
G
G
Instituto de Investigaciones Biomédicas Alberto Sols, Consejo Superior de Investigaciones Cientificas (CSIC)-Universidad Autónoma de Madrid (UAM), Arturo Duperier 4, E-28029, Madrid, Spain.
Leon
Y
Y
Gorospe
I
I
De Pablo
F
F
Alsina
B
B
Giraldez
F
F
Varela-Nieto
I
I
D000818:Animals; D002454:Cell Differentiation / Q000502:physiology*; D002642:Chick Embryo; D004423:Ear / Q000196:embryology; D005724:Ganglia / Q000196:embryology*; D007334:Insulin-Like Growth Factor I / Q000378:metabolism*
D007334:Insulin-Like Growth Factor I