Rgs4 is a regulator of mTOR activity required for motoneuron axon outgrowth and neuronal development in zebrafish

Abstract The Regulator of G protein signaling 4 (Rgs4) is a member of the RGS proteins superfamily that modulates the activity of G-protein coupled receptors. It is mainly expressed in the nervous system and is linked to several neuronal signaling pathways; however, its role in neural development in...

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Autores principales:	Aya Mikdache, Marie-José Boueid, Lorijn van der Spek, Emilie Lesport, Brigitte Delespierre, Julien Loisel-Duwattez, Cindy Degerny, Marcel Tawk
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/ae7d4224c42a4f8bbfeb4badcf76ef5e
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spelling	oai:doaj.org-article:ae7d4224c42a4f8bbfeb4badcf76ef5e2021-12-02T16:07:05ZRgs4 is a regulator of mTOR activity required for motoneuron axon outgrowth and neuronal development in zebrafish10.1038/s41598-021-92758-z2045-2322https://doaj.org/article/ae7d4224c42a4f8bbfeb4badcf76ef5e2021-06-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-92758-zhttps://doaj.org/toc/2045-2322Abstract The Regulator of G protein signaling 4 (Rgs4) is a member of the RGS proteins superfamily that modulates the activity of G-protein coupled receptors. It is mainly expressed in the nervous system and is linked to several neuronal signaling pathways; however, its role in neural development in vivo remains inconclusive. Here, we generated and characterized a rgs4 loss of function model (MZrgs4) in zebrafish. MZrgs4 embryos showed motility defects and presented reduced head and eye sizes, reflecting defective motoneurons axon outgrowth and a significant decrease in the number of neurons in the central and peripheral nervous system. Forcing the expression of Rgs4 specifically within motoneurons rescued their early defective outgrowth in MZrgs4 embryos, indicating an autonomous role for Rgs4 in motoneurons. We also analyzed the role of Akt, Erk and mechanistic target of rapamycin (mTOR) signaling cascades and showed a requirement for these pathways in motoneurons axon outgrowth and neuronal development. Drawing on pharmacological and rescue experiments in MZrgs4, we provide evidence that Rgs4 facilitates signaling mediated by Akt, Erk and mTOR in order to drive axon outgrowth in motoneurons and regulate neuronal numbers.Aya MikdacheMarie-José BoueidLorijn van der SpekEmilie LesportBrigitte DelespierreJulien Loisel-DuwattezCindy DegernyMarcel TawkNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-18 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Aya Mikdache Marie-José Boueid Lorijn van der Spek Emilie Lesport Brigitte Delespierre Julien Loisel-Duwattez Cindy Degerny Marcel Tawk Rgs4 is a regulator of mTOR activity required for motoneuron axon outgrowth and neuronal development in zebrafish
description	Abstract The Regulator of G protein signaling 4 (Rgs4) is a member of the RGS proteins superfamily that modulates the activity of G-protein coupled receptors. It is mainly expressed in the nervous system and is linked to several neuronal signaling pathways; however, its role in neural development in vivo remains inconclusive. Here, we generated and characterized a rgs4 loss of function model (MZrgs4) in zebrafish. MZrgs4 embryos showed motility defects and presented reduced head and eye sizes, reflecting defective motoneurons axon outgrowth and a significant decrease in the number of neurons in the central and peripheral nervous system. Forcing the expression of Rgs4 specifically within motoneurons rescued their early defective outgrowth in MZrgs4 embryos, indicating an autonomous role for Rgs4 in motoneurons. We also analyzed the role of Akt, Erk and mechanistic target of rapamycin (mTOR) signaling cascades and showed a requirement for these pathways in motoneurons axon outgrowth and neuronal development. Drawing on pharmacological and rescue experiments in MZrgs4, we provide evidence that Rgs4 facilitates signaling mediated by Akt, Erk and mTOR in order to drive axon outgrowth in motoneurons and regulate neuronal numbers.
format	article
author	Aya Mikdache Marie-José Boueid Lorijn van der Spek Emilie Lesport Brigitte Delespierre Julien Loisel-Duwattez Cindy Degerny Marcel Tawk
author_facet	Aya Mikdache Marie-José Boueid Lorijn van der Spek Emilie Lesport Brigitte Delespierre Julien Loisel-Duwattez Cindy Degerny Marcel Tawk
author_sort	Aya Mikdache
title	Rgs4 is a regulator of mTOR activity required for motoneuron axon outgrowth and neuronal development in zebrafish
title_short	Rgs4 is a regulator of mTOR activity required for motoneuron axon outgrowth and neuronal development in zebrafish
title_full	Rgs4 is a regulator of mTOR activity required for motoneuron axon outgrowth and neuronal development in zebrafish
title_fullStr	Rgs4 is a regulator of mTOR activity required for motoneuron axon outgrowth and neuronal development in zebrafish
title_full_unstemmed	Rgs4 is a regulator of mTOR activity required for motoneuron axon outgrowth and neuronal development in zebrafish
title_sort	rgs4 is a regulator of mtor activity required for motoneuron axon outgrowth and neuronal development in zebrafish
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/ae7d4224c42a4f8bbfeb4badcf76ef5e
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Rgs4 is a regulator of mTOR activity required for motoneuron axon outgrowth and neuronal development in zebrafish

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