Complementary and distinct roles of autophagy, apoptosis and senescence during early inner ear development.

The development of the inner ear complex cytoarchitecture and functional geometry requires the exquisite coordination of a variety of cellular processes in a temporal manner. At early stages of inner ear development several rounds of cell proliferation in the otocyst promote the growth of the structure. The apoptotic program is initiated in exceeding cells to adjust cell type numbers. Apoptotic cells are cleared by phagocytic cells that recognize the phosphatidylserine residues exposed in the cell membrane thanks to the energy supplied by autophagy. Specific molecular programs determine hair and supporting cell fate, these populations are responsible for the functions of the adult sensory organ: detection of sound, position and acceleration. The neurons that transmit auditory and balance information to the brain are also born at the otocyst by neurogenesis facilitated by autophagy. Cellular senescence participates in tissue repair, cancer and aging, situations in which cells enter a permanent cell cycle arrest and acquire a highly secretory phenotype that modulates their microenvironment. More recently, senescence has also been proposed to take place during vertebrate development in a limited number of transitory structures and organs; among the later, the endolymphatic duct in the inner ear. Here, we review these cellular processes during the early development of the inner ear, focusing on how the most recently described cellular senescence participates and cooperates with proliferation, apoptosis and autophagy to achieve otic morphogenesis and differentiation.