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ZFIN ID: ZDB-PUB-071129-9
Ttrap is an essential modulator of Smad3-dependent Nodal signaling during zebrafish gastrulation and left-right axis determination
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.
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
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.