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

Abstract

Auditory and vestibular organs form the adult vertebrate inner ear, both contain highly differentiated and specialized sensory epithelia that receive sound and position stimuli, respectively, and convey information to the brain (Magariños et al., 2012). Sensory patches of the inner ear contain sensory cells of two types, outer and inner hair cells, several types of supporting cells and neurons (Magariños et al., 2012; Burns et al., 2015). These cells do not regenerate in adult mammals, despite it has been described that there are small populations of resident stem cells in the adult inner ear (Oshima et al., 2007). Both sensory organs have a common developmental origin in the sensory otic placode, a thickening of the ectoderm that invaginates towards the neural tube forming the otic cup, which later closes up and forms the otic vesicle, also named otocyst (Adam et al., 1998; Magariños et al., 2012). The otic vesicle is an embryonic transitory organ that contains the information required to generate most cells of the adult inner ear (Magariños et al., 2014). The otic vesicle can be explanted and the whole organ cultured in Review Article Complementary and distinct roles of autophagy, apoptosis and senescence during early inner ear development

Confluence of Cellular Degradation Pathways During Interdigital Tissue Remodeling in Embryonic Tetrapods

“…In the last decade, in contrast to the protective role played by cell senescence in adult organisms, areas of massive cell senescence were observed during embryonic development in structures undergoing remodeling processes, such as the embryonic heart, otic vesicle, neural roof plate, limb primordia, or the mesonephros (Storer et al, 2013;Muñoz-Espín et al, 2013;Lorda-Diez et al, 2015Varela-Nieto et al, 2019). It was proposed that cell senescence is primarily an embryonic process that is evolutionarily adapted to protect organisms from oncogenesis, premature aging and other cell stressors (Storer et al, 2013) via the elimination of unwanted or damaged cells (Muñoz-Espín and Serrano, 2014).…”

Otic Neurogenesis Is Regulated by TGFβ in a Senescence-Independent Manner

“…Cells with features of senescence have been identified in several transient anatomical structures in the developing embryo, and appear to play a role in shaping organogenesis (Muñoz-Espín et al, 2013;Storer et al, 2013;Davaapil et al, 2017;Gibaja et al, 2019;Rhinn et al, 2019;Varela-Nieto et al, 2019). However, to date, there is no report linking cellular senescence with neurogenic processes during embryogenesis.…”

“…Mechanistically, cellular senescence has been linked to the TGFβ/SMAD and PI3K/FOXO pathways. Particularly, the transforming growth factor-beta (TGFβ) signaling pathway has been described to be key in regulating programmed senescence in the context of the degenerating mesonephros (Muñoz-Espín et al, 2013) and inner ear morphogenesis (Gibaja et al, 2019;Varela-Nieto et al, 2019).…”

Ceramide Kinase Inhibition Blocks IGF-1-Mediated Survival of Otic Neurosensory Progenitors by Impairing AKT Phosphorylation

“…The otic vesicle, a transitory fluid-filled structure lined by a pseudo-stratified epithelium, is considered the primordium of the inner ear, as its epithelial cells differentiate and generate most of the cell types of the adult inner ear ( Torres and Giráldez, 1998 ; Fekete and Wu, 2002 ). The transition from otic progenitors to mature inner ear cells occurs through the spatiotemporal regulation of proliferation, differentiation, migration, apoptosis, senescence, and autophagic processes, which creates the highly organized architecture of the adult sensory organ ( Sánchez-Calderón et al, 2007 ; Varela-Nieto et al, 2019 ). The sensory epithelium, named the organ of Corti in mammals and the basilar papilla in birds, is connected to the brain through the VIIIth cranial nerve.…”