Differential effects on Xenopus development of interference with type IIA and type IIB activin receptors.
One candidate for a mesoderm-inducing factor in early amphibian development is activin, a member of the TGF beta family. Overexpression of a truncated form of an activin receptor Type IIB abolishes activin responsiveness and mesoderm formation in vivo. The Xenopus Type IIA activin receptor XSTK9 differs from the Type IIB receptor by 43 and 25% in extracellular and intracellular domains respectively, suggesting the possibility of different functions in vivo. In this paper, we compare the Type IIA receptor with the Type IIB to test such a possibility. Simple overexpression of the wild-type receptors reveals minimal differences, but experiments with dominant negative mutants of each receptor show qualitatively distinct effects. We show that while truncated (kinase domain-deleted) Type IIB receptors cause axial defects as previously described, truncated type IIA receptors cause formation of secondary axes, similar to those seen by overexpression of truncated receptors for BMP-4, another TGF beta family member. Furthermore, in animal cap assays, truncated type IIB receptors inhibit induction of all mesodermal markers tested, while truncated type IIA receptors suppress induction only of ventral markers; the anterior/dorsal marker goosecoid is virtually unaffected. The suppression of ventral development by the type IIA truncated receptor suggests either that the truncated Type IIA receptor interferes with ventral BMP pathways, or that activin signaling through the Type IIA receptor is necessary for ventral patterning.
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Division of Developmental Biology, National Institute for Medical Research, Ridgeway, London, UK.
Kavka
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Smith
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Green
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D029404:Activin Receptors; D000595:Amino Acid Sequence; D000818:Animals; D002352:Carrier Proteins; D003598:Cytoskeletal Proteins; D004268:DNA-Binding Proteins / Q000235:genetics; D018507:Gene Expression Regulation, Developmental; D051956:Goosecoid Protein; D018398:Homeodomain Proteins; D008648:Mesoderm / Q000166:cytology; D008969:Molecular Sequence Data; D009024:Morphogenesis; D020648:Peptide Elongation Factor 1; D010445:Peptide Elongation Factors / Q000235:genetics; D011506:Proteins / Q000235:genetics; D012333:RNA, Messenger / Q000235:genetics; D017978:Receptors, Growth Factor / Q000145:classification / Q000378:metabolism*; D012097:Repressor Proteins; D016415:Sequence Alignment; D013329:Structure-Activity Relationship; D014157:Transcription Factors; D051153:Wnt Proteins; D014982:Xenopus laevis / Q000196:embryology* / Q000235:genetics; D029961:Zebrafish Proteins; D000099176:Noggin Protein
D029404:Activin Receptors; D002352:Carrier Proteins; D003598:Cytoskeletal Proteins; D004268:DNA-Binding Proteins; D051956:Goosecoid Protein; D018398:Homeodomain Proteins; D020648:Peptide Elongation Factor 1; D010445:Peptide Elongation Factors; D011506:Proteins; D012333:RNA, Messenger; D017978:Receptors, Growth Factor; D012097:Repressor Proteins; D014157:Transcription Factors; D051153:Wnt Proteins; D029961:Zebrafish Proteins; D000099176:Noggin Protein; C094521:wnt8a protein, zebrafish