TY  - JOUR
A1  - Rodriguez Aburto, Maria
A1  - Sánchez-Calderón, Hortensia
A1  - Hurlé, Juan M.
A1  - Varela-Nieto, Isabel
A1  - Magariños, Marta
T1  - Early otic development depends on autophagy for apoptotic cell clearance and neural differentiation
T2  - Cell death and disease
N2  - Autophagy is a highly regulated program of self-degradation of the cytosolic constituents that has key roles during early development and in adult cell growth and homeostasis. To investigate the role of autophagy in otic neurogenesis, we studied the expression of autophagy genes in early stages of chicken (Gallus gallus) inner ear development and the consequences of inhibiting the autophagic pathway in organotypic cultures of explanted chicken otic vesicles (OVs). Here we show the expression of autophagy-related genes (Atg) Beclin-1 (Atg6), Atg5 and LC3B (Atg8) in the otocyst and the presence of autophagic vesicles by using transmission electron microscopy in the otic neurogenic zone. The inhibition of the transcription of LC3B by using antisense morpholinos and of class III phosphatidylinositol 3-kinase with 3-methyladenine causes an aberrant morphology of the OV with accumulation of apoptotic cells. Moreover, inhibition of autophagy provokes the misregulation of the cell cycle in the otic epithelium, impaired neurogenesis and poor axonal outgrowth. 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. Taken together, our results show for the first time that autophagy is an active and essential process during early inner ear development.
KW  - apoptosis
KW  - autophagy
KW  - 3-MA
KW  - otic neurogenesis
KW  - IGF-I
Y1  - 2012
UR  - http://publikationen.ub.uni-frankfurt.de/frontdoor/index/index/docId/30022
UR  - https://nbn-resolving.org/urn:nbn:de:hebis:30:3-300225
SN  - 2041-4889
N1  - Cell Death and Disease is an open-access journal published by Nature Publishing Group. This work is licensed under the Creative Commons Attribution-NonCommercial-No Derivative Works 3.0 Unported License. To view a copy of this license, visit http://creativecommons.org/licenses/by-nc-nd/3.0/
VL  - 3
IS  - 394
PB  - Nature Publishing Group
CY  - London [u.a.]
ER  -