PUBLICATION
Regulator of g protein signaling 3 modulates wnt5b calcium dynamics and somite patterning
- Authors
- Freisinger, C.M., Fisher, R.A., and Slusarski, D.C.
- ID
- ZDB-PUB-100719-56
- Date
- 2010
- Source
- PLoS Genetics 6(7): e1001020 (Journal)
- Registered Authors
- Slusarski, Diane C.
- Keywords
- Embryos, Somites, Zebrafish, Wnt signaling cascade, G-protein signaling, GTPase signaling, Calcium signaling, Developmental signaling
- MeSH Terms
-
- Animals
- Body Patterning*
- Calcium/analysis
- Calcium Signaling*
- Embryonic Development
- GTP-Binding Protein alpha Subunits, Gi-Go/metabolism
- GTPase-Activating Proteins/physiology
- Heterotrimeric GTP-Binding Proteins/metabolism
- Molecular Imaging
- RGS Proteins/analysis
- RGS Proteins/physiology*
- Signal Transduction/physiology
- Somites/embryology*
- Wnt Proteins/analysis
- Wnt Proteins/physiology*
- Zebrafish
- Zebrafish Proteins/analysis
- Zebrafish Proteins/physiology*
- PubMed
- 20628572 Full text @ PLoS Genet.
Citation
Freisinger, C.M., Fisher, R.A., and Slusarski, D.C. (2010) Regulator of g protein signaling 3 modulates wnt5b calcium dynamics and somite patterning. PLoS Genetics. 6(7):e1001020.
Abstract
Vertebrate development requires communication among cells of the embryo in order to define the body axis, and the Wnt-signaling network plays a key role in axis formation as well as in a vast array of other cellular processes. One arm of the Wnt-signaling network, the non-canonical Wnt pathway, mediates intracellular calcium release via activation of heterotrimeric G proteins. Regulator of G protein Signaling (RGS) proteins can accelerate inactivation of G proteins by acting as G protein GTPase-activating proteins (GAPs), however, the possible role of RGS proteins in non-canonical Wnt signaling and development is not known. Here, we identify rgs3 as having an overlapping expression pattern with wnt5b in zebrafish and reveal that individual knockdown of either rgs3 or wnt5b gene function produces similar somite patterning defects. Additionally, we describe endogenous calcium release dynamics in developing zebrafish somites and determine that both rgs3 and wnt5b function are required for appropriate frequency and amplitude of calcium release activity. Using rescue of gene knockdown and in vivo calcium imaging assays, we demonstrate that the activity of Rgs3 requires its ability to interact with Galpha subunits and function as a G protein GAP. Thus, Rgs3 function is necessary for appropriate frequency and amplitude of calcium release during somitogenesis and is downstream of Wnt5 activity. These results provide the first evidence for an essential developmental role of RGS proteins in modulating the duration of non-canonical Wnt signaling.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping