PUBLICATION

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

Authors
Mikdache, A., Boueid, M.J., van der Spek, L., Lesport, E., Delespierre, B., Loisel-Duwattez, J., Degerny, C., Tawk, M.
ID
ZDB-PUB-210629-12
Date
2021
Source
Scientific Reports   11: 13338 (Journal)
Registered Authors
Boueid, Marie-Jose, Degerny, Cindy, Tawk, Marcel
Keywords
none
MeSH Terms
  • Animals
  • Axons/metabolism
  • Motor Neurons/metabolism*
  • Neurogenesis/physiology*
  • Neuronal Outgrowth/physiology*
  • Neurons, Efferent/metabolism
  • RGS Proteins/metabolism*
  • Signal Transduction/physiology
  • TOR Serine-Threonine Kinases/metabolism*
  • Zebrafish/metabolism*
PubMed
34172795 Full text @ Sci. Rep.
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.
Genes / Markers
Figures
Expression
Phenotype
Mutation and Transgenics
Human Disease / Model Data
Sequence Targeting Reagents
Fish
Antibodies
Orthology
Engineered Foreign Genes
Mapping
Errata and Notes