Rgs4 is a regulator of mTOR activity required for motoneuron axon outgrowth and neuronal development in zebrafish
| Autor: | Cindy Degerny, Lorijn van der Spek, Marie-José Boueid, Brigitte Delespierre, Aya Mikdache, Marcel Tawk, Emilie Lesport, Julien Loisel-Duwattez |
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| Rok vydání: | 2020 |
| Předmět: |
Nervous system
Science Neurogenesis Neuronal Outgrowth Article RGS4 Regulator of G protein signaling Neurons Efferent Developmental biology medicine Animals Mechanistic target of rapamycin Protein kinase B Zebrafish PI3K/AKT/mTOR pathway Motor Neurons Multidisciplinary biology TOR Serine-Threonine Kinases biology.organism_classification Axons Cell biology medicine.anatomical_structure nervous system biology.protein Medicine Neural development RGS Proteins Signal Transduction Neuroscience |
| Zdroj: | Scientific Reports Scientific Reports, Vol 11, Iss 1, Pp 1-18 (2021) |
| ISSN: | 2045-2322 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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