Growth factors and early development of otic neurons: Interactions between intrinsic and extrinsic signals

The interplay between intrinsic and extrinsic factors is essential for the transit into different cell states during development. Secreted factors mediate crucial steps in development such as cell growth and survival, bias between self-renewal and differentiation, or choices between different cell fates. Three families of growth factors emerge as critical for early steps in otic neurogenesis: fibroblast growth factors (FGFs); nerve growth factor (NGF)-related neurotrophins (NTs); and insulin-related factors, particularly insulin-like growth factor-1 (IGF-1). Otic neurons connect the sensory mechanoreceptors of the ear, the hair cells, with their targets in the central nervous system (CNS). The generation of otic neurons is a sequential process that includes first the specification of otic precursors in the otic epithelium, second the delamination of epithelial neuroblasts to form the cochleovestibular ganglion (CVG), third the proliferative expansion of ganglionar neuroblasts, and finally the differentiation of neurons that innervate back the vestibular and cochlear (auditory) sensory organs. Each step is characterized by the expression of a particular set of transcription factors and differentially regulated by growth factor signaling, based on which a simple model for early otic neurogenesis is proposed. © 2003 Elsevier Inc. All rights reserved.