BUSCADOR RECOLECTA

Digital.CSIC. Repositorio Institucional del CSIC

oai:digital.csic.es:10261/180157

Embryonic development requires the coordinated regulation of apoptosis, survival, autophagy, proliferation and differentiation programs. Senescence has recently joined the cellular processes required to master development, in addition to its well-described roles in cancer and ageing. Here, we show that senescent cells are present in a highly regulated temporal pattern in the developing vertebrate inner ear, first, surrounding the otic pore and, later, in the otocyst at the endolymphatic duct. Cellular senescence is associated with areas of increased apoptosis and reduced proliferation consistent with the induction of the process when the endolymphatic duct is being formed. Modulation of senescence disrupts otic vesicle morphology. Transforming growth factor beta (TGFβ) signaling interacts with signaling pathways elicited by insulin-like growth factor type 1 (IGF-1) to jointly coordinate cellular dynamics required for morphogenesis and differentiation. Taken together, these results show that senescence is a natural occurring process essential for early inner ear development., This work was supported by the European Commission FP7-PEOPLE-2013-IAPP TARGEAR to IVN and by the Spanish MINECO/FEDER SAF2017-86107-R to IVN and MM. SP was supported by a FPI predoctoral fellowship (BES-2015-071311) funded by MINECO/European Social Fund., Peer reviewed