The verterbrate inner ear is an excellent model system to study signalling mechanisms
in embryonic development. During the last years, insulin-like growth factor-I (IGF-I)
has attracted attention in relation to the regulation of inner ear ontogenesis. IGF-I
and its high-affinity tyrosine-kinase receptor are expressed during early stages of
inner ear development. IGF-I is a powerful mitogen for the otic vesicle, where it
stimulates cell-division and mitogenic signalling cascades. Later in development,
IGF-I also promotes survival and neurogenesis of the otic neurones in the cochleovestibular
ganglion (CVG). The actions of IGF-I are associated with the generation of lipidic
messengers and the activation of Raf kinase, which results in the rapid induction
of the expression of the proliferative cell nuclear antigen (PCNA) and the nuclear
proto-oncogenes c-fos and c-jun. Regulation of organogenesis involves a dynamic balance of the mechanisms regulating
cell division, differentiation and death. A model is proposed where this balance is
the consequence of the action of IGF-I and NGF, which converge in Raf activation or
suppression. The combinatorial expression of Jun and Fos family members in particular
domains of the otic vesicle would be the final result of such cascade. Some of these
mechanisms may be also implicated in otic regeneration.
Key words
AP-1 Complex - Development - NGF - Lipidic Messengers - Organotypic Cultures
