PUBLICATION
Ttrap is an essential modulator of Smad3-dependent Nodal signaling during zebrafish gastrulation and left-right axis determination
- Authors
- Esguerra, C.V., Nelles, L., Vermeire, L., Ibrahimi, A., Crawford, A.D., Derua, R., Janssens, E., Waelkens, E., Carmeliet, P., Collen, D., and Huylebroeck, D.
- ID
- ZDB-PUB-071129-9
- Date
- 2007
- Source
- Development (Cambridge, England) 134(24): 4381-4393 (Journal)
- Registered Authors
- Crawford, Alexander, Esguerra, Camila V.
- Keywords
- Alk4, E-cadherin, Gastrulation, Left-right asymmetry, Node, Smad
- MeSH Terms
-
- Activin Receptors/genetics
- Activin Receptors/metabolism
- Activin Receptors, Type I
- Animals
- Base Sequence
- Body Patterning/genetics
- Body Patterning/physiology
- Cadherins/genetics
- Cadherins/metabolism
- DNA Primers/genetics
- Gastrulation/genetics
- Gastrulation/physiology
- Gene Expression Regulation, Developmental
- Nodal Protein
- Oligoribonucleotides, Antisense/genetics
- Signal Transduction
- Smad3 Protein/genetics
- Smad3 Protein/metabolism*
- Transcription Factors/genetics
- Transcription Factors/metabolism
- Transforming Growth Factor beta/genetics
- Transforming Growth Factor beta/metabolism*
- Tumor Necrosis Factor Receptor-Associated Peptides and Proteins/genetics
- Tumor Necrosis Factor Receptor-Associated Peptides and Proteins/metabolism*
- Zebrafish/embryology*
- Zebrafish/genetics
- Zebrafish/metabolism*
- Zebrafish Proteins/genetics
- Zebrafish Proteins/metabolism*
- PubMed
- 18039968 Full text @ Development
Citation
Esguerra, C.V., Nelles, L., Vermeire, L., Ibrahimi, A., Crawford, A.D., Derua, R., Janssens, E., Waelkens, E., Carmeliet, P., Collen, D., and Huylebroeck, D. (2007) Ttrap is an essential modulator of Smad3-dependent Nodal signaling during zebrafish gastrulation and left-right axis determination. Development (Cambridge, England). 134(24):4381-4393.
Abstract
During vertebrate development, signaling by the TGFbeta ligand Nodal is critical for mesoderm formation, correct positioning of the anterior-posterior axis, normal anterior and midline patterning, and left-right asymmetric development of the heart and viscera. Stimulation of Alk4/EGF-CFC receptor complexes by Nodal activates Smad2/3, leading to left-sided expression of target genes that promote asymmetric placement of certain internal organs. We identified Ttrap as a novel Alk4- and Smad3-interacting protein that controls gastrulation movements and left-right axis determination in zebrafish. Morpholino-mediated Ttrap knockdown increases Smad3 activity, leading to ectopic expression of snail1a and apparent repression of e-cadherin, thereby perturbing cell movements during convergent extension, epiboly and node formation. Thus, although the role of Smad proteins in mediating Nodal signaling is well-documented, the functional characterization of Ttrap provides insight into a novel Smad partner that plays an essential role in the fine-tuning of this signal transduction cascade.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping