Structural and functional evidence for a singular repertoire of BMP receptor signal transducing proteins in the lophotrochozoan Crassostrea gigas suggests a shared ancestral BMP/activin pathway.
The transforming growth factor beta (TGF-beta) superfamily includes bone morphogenetic proteins, activins and TGF-betasensu stricto (s.s). These ligands, which transduce their signal through a heteromeric complex of type I and type II receptors, have been shown to play a key role in numerous biological processes including early embryonic development in both deuterostomes and ecdyzozoans. Lophochotrozoans, the third major group of bilaterian animals, have remained in the background of the molecular survey of metazoan development. We report the cloning and functional study of the central part of the BMP pathway machinery in the bivalve mollusc Crassostrea gigas (Cg-BMPR1 type I receptor and Cg-TGFbetasfR2 type II receptor), showing an unusual functional mode of signal transduction for this superfamily. The use of the zebrafish embryo as a reporter organism revealed that Cg-BMPR1, Cg-TGFbetasfR2, Cg-ALR I, an activin Type I receptor or their dominant negative acting truncated forms, when overexpressed during gastrulation, resulted in a range of phenotypes displaying severe disturbance of anterioposterior patterning, due to strong modulations of ventrolateral mesoderm patterning. The results suggest that Cg-BMPR1, and to a certain degree Cg-TGFbetasfR2 proteins, function in C. gigas in a similar way to their zebrafish orthologues. Finally, based on phylogenetic analyses, we propose an evolutionary model within the complete TGF-beta superfamily. Thus, evidence provided by this study argues for a possible conserved endomesoderm/ectomesoderm inductive mechanism in spiralians through an ancestral BMP/activin pathway in which the singular, promiscuous and probably unique Cg-TGFbetasfR2 would be the shared type II receptor interface for both BMP and activin ligands.
Sars International Centre for Marine Molecular Biology, High Technology Centre, Bergen, Norway. amaury.herpin@biozentrum.uni-wuerzburg.de
Amaury
A
Herpin
Christophe
C
Lelong
Thomas
T
Becker
Frederic
F
Rosa
Pascal
P
Favrel
Charles
C
Cunningham
D030201:Activin Receptors, Type I / Q000235:genetics / Q000378:metabolism; D028341:Activins / Q000378:metabolism*; D000595:Amino Acid Sequence; D000818:Animals; D005075:Biological Evolution; D019521:Body Patterning; D052005:Bone Morphogenetic Protein Receptors, Type I; D019485:Bone Morphogenetic Proteins / Q000378:metabolism*; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism; D018507:Gene Expression Regulation, Developmental; D005799:Genes, Dominant; D007814:Larva / Q000166:cytology / Q000378:metabolism; D008648:Mesoderm / Q000166:cytology / Q000378:metabolism; D008969:Molecular Sequence Data; D009363:Neoplasm Proteins / Q000235:genetics / Q000378:metabolism; D010125:Ostreidae / Q000196:embryology / Q000235:genetics* / Q000378:metabolism; D010641:Phenotype; D010802:Phylogeny; D017346:Protein Serine-Threonine Kinases / Q000235:genetics / Q000378:metabolism*; D000077294:Receptor, Transforming Growth Factor-beta Type II; D017978:Receptors, Growth Factor / Q000235:genetics / Q000378:metabolism*; D018125:Receptors, Transforming Growth Factor beta / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction; D016212:Transforming Growth Factor beta / Q000378:metabolism / Q000494:pharmacology; D015027:Zebrafish / Q000196:embryology / Q000378:metabolism
D019485:Bone Morphogenetic Proteins; D004268:DNA-Binding Proteins; C120898:KMT2D protein, human; D009363:Neoplasm Proteins; D017978:Receptors, Growth Factor; D018125:Receptors, Transforming Growth Factor beta; D016212:Transforming Growth Factor beta; D028341:Activins; D017346:Protein Serine-Threonine Kinases; D030201:Activin Receptors, Type I; D052005:Bone Morphogenetic Protein Receptors, Type I; D000077294:Receptor, Transforming Growth Factor-beta Type II