Ttrap is an essential modulator of Smad3-dependent Nodal signaling during zebrafish gastrulation and left-right axis determination.
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.
Esguerra
Camila V
CV
Center for Transgene Technology and Gene Therapy, VIB, Herestraat 49, B-3000 Leuven, Belgium. camila.esguerra@med.kuleuven.be
Nelles
Luc
L
Vermeire
Liesbeth
L
Ibrahimi
Abdelilah
A
Crawford
Alexander D
AD
Derua
Rita
R
Janssens
Els
E
Waelkens
Etienne
E
Carmeliet
Peter
P
Collen
Desiré
D
Huylebroeck
Danny
D
D029404:Activin Receptors / Q000235:genetics / Q000378:metabolism; D030201:Activin Receptors, Type I; D000818:Animals; D001483:Base Sequence; D019521:Body Patterning / Q000235:genetics / Q000502:physiology; D015820:Cadherins / Q000235:genetics / Q000378:metabolism; D017931:DNA Primers / Q000235:genetics; D054262:Gastrulation / Q000235:genetics / Q000502:physiology; D018507:Gene Expression Regulation, Developmental; D055457:Nodal Protein; D020320:Oligoribonucleotides, Antisense / Q000235:genetics; D015398:Signal Transduction; D051900:Smad3 Protein / Q000235:genetics / Q000378:metabolism*; D000071250:Snail Family Transcription Factors; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism; D016212:Transforming Growth Factor beta / Q000235:genetics / Q000378:metabolism*; D047988:Tumor Necrosis Factor Receptor-Associated Peptides and Proteins / Q000235:genetics / Q000378:metabolism*; D015027:Zebrafish / Q000196:embryology* / Q000235:genetics / Q000378:metabolism*; D029961:Zebrafish Proteins / Q000235:genetics / Q000378:metabolism*
D015820:Cadherins; D017931:DNA Primers; D055457:Nodal Protein; D020320:Oligoribonucleotides, Antisense; D051900:Smad3 Protein; D000071250:Snail Family Transcription Factors; D014157:Transcription Factors; D016212:Transforming Growth Factor beta; D047988:Tumor Necrosis Factor Receptor-Associated Peptides and Proteins; D029961:Zebrafish Proteins; C514487:snai1a protein, zebrafish; D029404:Activin Receptors; D030201:Activin Receptors, Type I; C512426:acvr1ba protein, zebrafish