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MANF Is Essential for Neurite Extension and Neuronal Migration in the Developing Cortex

Mesencephalic astrocyte-derived neurotrophic factor (MANF) is an endoplasmic reticulum (ER) resident protein with neuroprotective effects. Previous studies have shown that MANF expression is altered in the developing rodent cortex in a spatiotemporal manner. However, the role of MANF in mammalian ne...

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Autores principales: Tseng, Kuan-Yin, Danilova, Tatiana, Domanskyi, Andrii, Saarma, Mart, Lindahl, Maria, Airavaara, Mikko
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Society for Neuroscience 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5655607/
https://www.ncbi.nlm.nih.gov/pubmed/29082311
http://dx.doi.org/10.1523/ENEURO.0214-17.2017
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author Tseng, Kuan-Yin
Danilova, Tatiana
Domanskyi, Andrii
Saarma, Mart
Lindahl, Maria
Airavaara, Mikko
author_facet Tseng, Kuan-Yin
Danilova, Tatiana
Domanskyi, Andrii
Saarma, Mart
Lindahl, Maria
Airavaara, Mikko
author_sort Tseng, Kuan-Yin
collection PubMed
description Mesencephalic astrocyte-derived neurotrophic factor (MANF) is an endoplasmic reticulum (ER) resident protein with neuroprotective effects. Previous studies have shown that MANF expression is altered in the developing rodent cortex in a spatiotemporal manner. However, the role of MANF in mammalian neurogenesis is not known. The aim of this study was to determine the role of MANF in neural stem cell (NSC) proliferation, differentiation, and cerebral cortex development. We found that MANF is highly expressed in neural lineage cells, including NSCs in the developing brain. We discovered that MANF-deficient NSCs in culture are viable and show no defect in proliferation. However, MANF-deficient cells have deficits in neurite extension upon neuronal differentiation. In vivo, MANF removal leads to slower neuronal migration and impaired neurite outgrowth. In vitro, mechanistic studies indicate that impaired neurite growth is preceded by reduced de novo protein synthesis and constitutively activated unfolded protein response (UPR) pathways. This study is the first to demonstrate that MANF is a novel and critical regulator of neurite growth and neuronal migration in mammalian cortical development.
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spelling pubmed-56556072017-10-27 MANF Is Essential for Neurite Extension and Neuronal Migration in the Developing Cortex Tseng, Kuan-Yin Danilova, Tatiana Domanskyi, Andrii Saarma, Mart Lindahl, Maria Airavaara, Mikko eNeuro New Research Mesencephalic astrocyte-derived neurotrophic factor (MANF) is an endoplasmic reticulum (ER) resident protein with neuroprotective effects. Previous studies have shown that MANF expression is altered in the developing rodent cortex in a spatiotemporal manner. However, the role of MANF in mammalian neurogenesis is not known. The aim of this study was to determine the role of MANF in neural stem cell (NSC) proliferation, differentiation, and cerebral cortex development. We found that MANF is highly expressed in neural lineage cells, including NSCs in the developing brain. We discovered that MANF-deficient NSCs in culture are viable and show no defect in proliferation. However, MANF-deficient cells have deficits in neurite extension upon neuronal differentiation. In vivo, MANF removal leads to slower neuronal migration and impaired neurite outgrowth. In vitro, mechanistic studies indicate that impaired neurite growth is preceded by reduced de novo protein synthesis and constitutively activated unfolded protein response (UPR) pathways. This study is the first to demonstrate that MANF is a novel and critical regulator of neurite growth and neuronal migration in mammalian cortical development. Society for Neuroscience 2017-09-29 /pmc/articles/PMC5655607/ /pubmed/29082311 http://dx.doi.org/10.1523/ENEURO.0214-17.2017 Text en Copyright © 2017 Tseng et al. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution 4.0 International license (http://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, distribution and reproduction in any medium provided that the original work is properly attributed.
spellingShingle New Research
Tseng, Kuan-Yin
Danilova, Tatiana
Domanskyi, Andrii
Saarma, Mart
Lindahl, Maria
Airavaara, Mikko
MANF Is Essential for Neurite Extension and Neuronal Migration in the Developing Cortex
title MANF Is Essential for Neurite Extension and Neuronal Migration in the Developing Cortex
title_full MANF Is Essential for Neurite Extension and Neuronal Migration in the Developing Cortex
title_fullStr MANF Is Essential for Neurite Extension and Neuronal Migration in the Developing Cortex
title_full_unstemmed MANF Is Essential for Neurite Extension and Neuronal Migration in the Developing Cortex
title_short MANF Is Essential for Neurite Extension and Neuronal Migration in the Developing Cortex
title_sort manf is essential for neurite extension and neuronal migration in the developing cortex
topic New Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5655607/
https://www.ncbi.nlm.nih.gov/pubmed/29082311
http://dx.doi.org/10.1523/ENEURO.0214-17.2017
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