Role of IGF-1 as an autophagy regulator during otic vesicle development

Abstract

The otic vesicle is an autonomous embryonic structure that contains the information required to generate most of the cellular types that shape the adult inner ear. Otic vesicle development involves different processes including apoptosis, proliferation, senescence, cell differentiation and autophagy. Autophagy is a highly conserved catabolic process essential for vertebrate embryonic development and adult homeostasis. Insulin-like growth factor-1 (IGF-1) is a key element in chicken otic development, and its deficit causes syndromic deafness in mice and men. IGF-1 regulates autophagy both negatively and positively depending on the cellular context. Here we have studied if IGF-1 regulates autophagy during otic vesicle development. The experiments were performed in ex vivo cultures of chicken otocysts treated with autophagy modulators (Bafilomycin A1 and Rapamicyn), IGF-1R inhibitors and IGF-1. Our results show that IGF-1 signaling via high affinity IGF1R promotes survival during early otic development. Autophagy is an essential process to carry out developmental apoptosis and it is negatively regulated by IGF-1. IGF-1 via IGF1R increases the number of neuroblasts and their differentiation.