Regulation of nodal signalling and mesendoderm formation by TARAM-A, a TGFbeta-related type I receptor.
Nodal signalling is essential for many developmental events during vertebrate development, including the establishment of left-right asymmetry, of dorsoventral axis of the central nervous system, and endoderm and mesoderm formation. The zebrafish TGFbeta-related type I receptor, TARAM-A (Tar), is expressed in the prospective mesendodermal territory and, when activated, can transfate early blastomeres into endoderm, suggesting that Nodal and Tar may represent similar signalling pathways. We have analysed the functional relationships between those two pathways in zebrafish. We first demonstrate that tar and the zebrafish nodal genes cyc and sqt functionally interact. We also show that a dominant-negative isoform of Tar, TarMR, interferes specifically with the function of Cyc and Sqt in vitro, but does not interfere with the function of BMP2, another TGFbeta-related molecule. TarMR interferes also with Nodal signalling in vivo since it enhances the phenotype of embryos with weakened Nodal signalling. Overexpression of tarMR in wild-type embryos interfered with the formation of endoderm-derived structures. Conversely, overexpression of tar enlarged the presumptive mesendodermal region at the onset of gastrulation. Together, our results point to Tar as an essential factor for endoderm formation and an important modulator of Nodal signalling, potentially representing one of the Nodal receptors. (c)2001 Elsevier Science.
Aoki
Tazu O
TO
U368 INSERM, Ecole Normale Supérieure, 46 rue d'Ulm, 75230 Paris, France.
Mathieu
Juliette
J
Saint-Etienne
Laure
L
Rebagliati
Michael R
MR
Peyriéras
Nadine
N
Rosa
Frédéric M
FM
D028341:Activins / Q000378:metabolism; D000818:Animals; D015415:Biomarkers; D019521:Body Patterning / Q000235:genetics / Q000502:physiology*; D019485:Bone Morphogenetic Proteins / Q000502:physiology; D004625:Embryo, Nonmammalian / Q000502:physiology; D004707:Endoderm / Q000502:physiology*; D018507:Gene Expression Regulation, Developmental; D005799:Genes, Dominant; D018398:Homeodomain Proteins / Q000235:genetics / Q000502:physiology; D047908:Intracellular Signaling Peptides and Proteins; D008648:Mesoderm / Q000502:physiology*; D016296:Mutagenesis; D055457:Nodal Protein; D055456:Nodal Signaling Ligands; D010641:Phenotype; D017346:Protein Serine-Threonine Kinases; D018125:Receptors, Transforming Growth Factor beta / Q000235:genetics / Q000502:physiology*; D011993:Recombinant Fusion Proteins / Q000502:physiology; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction / Q000235:genetics / Q000502:physiology*; D014157:Transcription Factors / Q000235:genetics / Q000502:physiology; D016212:Transforming Growth Factor beta / Q000235:genetics / Q000502:physiology*; D015027:Zebrafish / Q000196:embryology / Q000235:genetics; D029961:Zebrafish Proteins
D015415:Biomarkers; D019485:Bone Morphogenetic Proteins; D018398:Homeodomain Proteins; D047908:Intracellular Signaling Peptides and Proteins; D055457:Nodal Protein; D055456:Nodal Signaling Ligands; D018125:Receptors, Transforming Growth Factor beta; D011993:Recombinant Fusion Proteins; D014157:Transcription Factors; D016212:Transforming Growth Factor beta; D029961:Zebrafish Proteins; C485171:ndr1 protein, zebrafish; C512832:ndr2 protein, zebrafish; C110484:tdgf1 protein, zebrafish; D028341:Activins; D017346:Protein Serine-Threonine Kinases