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.
Publication types
-
Research Support, Non-U.S. Gov't
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*
-
Snail Family Transcription Factors
-
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*
Substances
-
Cadherins
-
DNA Primers
-
Nodal Protein
-
Oligoribonucleotides, Antisense
-
Smad3 Protein
-
Snail Family Transcription Factors
-
Transcription Factors
-
Transforming Growth Factor beta
-
Tumor Necrosis Factor Receptor-Associated Peptides and Proteins
-
Zebrafish Proteins
-
snai1a protein, zebrafish
-
Activin Receptors
-
Activin Receptors, Type I
-
acvr1ba protein, zebrafish