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Early otic development depends on autophagy for apoptotic cell clearance and neural differentiation
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 c...
Autores principales: | , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Nature Publishing Group
2012
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3481121/ https://www.ncbi.nlm.nih.gov/pubmed/23034329 http://dx.doi.org/10.1038/cddis.2012.132 |
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author | Aburto, M R Sánchez-Calderón, H Hurlé, J M Varela-Nieto, I Magariños, M |
author_facet | Aburto, M R Sánchez-Calderón, H Hurlé, J M Varela-Nieto, I Magariños, M |
author_sort | Aburto, M R |
collection | PubMed |
description | 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. |
format | Online Article Text |
id | pubmed-3481121 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2012 |
publisher | Nature Publishing Group |
record_format | MEDLINE/PubMed |
spelling | pubmed-34811212012-10-26 Early otic development depends on autophagy for apoptotic cell clearance and neural differentiation Aburto, M R Sánchez-Calderón, H Hurlé, J M Varela-Nieto, I Magariños, M Cell Death Dis Original Article 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. Nature Publishing Group 2012-10 2012-10-04 /pmc/articles/PMC3481121/ /pubmed/23034329 http://dx.doi.org/10.1038/cddis.2012.132 Text en Copyright © 2012 Macmillan Publishers Limited http://creativecommons.org/licenses/by-nc-nd/3.0/ 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/ |
spellingShingle | Original Article Aburto, M R Sánchez-Calderón, H Hurlé, J M Varela-Nieto, I Magariños, M Early otic development depends on autophagy for apoptotic cell clearance and neural differentiation |
title | Early otic development depends on autophagy for apoptotic cell clearance and neural differentiation |
title_full | Early otic development depends on autophagy for apoptotic cell clearance and neural differentiation |
title_fullStr | Early otic development depends on autophagy for apoptotic cell clearance and neural differentiation |
title_full_unstemmed | Early otic development depends on autophagy for apoptotic cell clearance and neural differentiation |
title_short | Early otic development depends on autophagy for apoptotic cell clearance and neural differentiation |
title_sort | early otic development depends on autophagy for apoptotic cell clearance and neural differentiation |
topic | Original Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3481121/ https://www.ncbi.nlm.nih.gov/pubmed/23034329 http://dx.doi.org/10.1038/cddis.2012.132 |
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