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Early otic development depends on autophagy for apoptotic cell clearance and neural differentiation

AuthorsMagariños, Marta ; Rodríguez Aburto, María ; Sánchez-Calderón, Hortensia; Hurlé, Juan M.; Varela-Nieto, Isabel
Issue Date2012
CitationIEB (2012)
Abstract[Introduction]: Early inner ear development requires a strict regulation of the dynamics of cellular proliferation, survival, migration and differentiation in order to generate the different cell types of the adult inner ear, including the neurons for the acoustic-vestibular ganglion. Autophagy is a program of self-degradation of the cytosolic constituents crucial for balancing sources of energy in response to different extracellular stimuli. In vertebrates, autophagy is a highly regulated process that plays key roles during early development and in adult cell growth and homeostasis. [Material and Methods]: To investigate the role of autophagy in the developing inner ear we have studied the expression of autophagy genes in early stages of otic development and the consequences of inhibiting farmacologically and genetically the autophagic pathway in organotypic cultures of explanted chicken otic vesicles. [Results]: Here we show the expression of Beclin-1, Atg5 and LC3B in the otocyst and the presence of autophagic vesicles by using transmission electron microscopy in the otic neurogenic zone. The inhibition of autophagy causes accumulation of apoptotic cells and missregulation of the cell cycle at the otic epithelia. Moreover, neurogenesis is severely impaired, thus the number of neural cells decreases and axonal outgrowth is reduced. Finally, our results indicate that autophagy provides the energy required for the clearing of neuroepithelial dying cells and suggest that it is required for the migration of otic neuronal precursors. [Conclusions]: Taken together, our results show for the first time that autophagy is an active and essential process during early inner ear development.
DescriptionComunicación presentada al 49th Workshop on Inner Ear Biology celebrada en Alemania del 30 de septiembre al 2 de octubre de 2012.
Appears in Collections:(IIBM) Comunicaciones congresos
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