BMP signaling is required for heart formation in vertebrates.
In these studies, we have taken advantage of a transient transgenic strategy in Xenopus embryos to demonstrate that BMP signaling is required in vivo for heart formation in vertebrates. Ectopic expression of dominant negative Type I (tALK3) or Type II (tBMPRII) BMP receptors in developing Xenopus embryos results in reduction or absence of heart formation. Additionally, blocking BMP signaling in this manner downregulates expression of XNkx2-5, a homeobox gene required for cardiac specification, prior to differentiation. Notably, however, initial expression of XNkx2-5 is not affected. Mutant phenotypes can be rescued by co-injection of mutant with wild-type receptors or co-injection of mutant receptors with XSmad1, a downstream mediator of BMP signaling. Whole-mount in situ analyses indicate that ALK3 and XSmad1 are coexpressed in cardiogenic regions. Together, our results demonstrate that BMP signaling is required for maintenance of XNkx2-5 expression and heart formation and suggest that ALK3, BMPRII, and XSmad1 may mediate this signaling.
Department of Medicine, University of California at San Diego, 92093-0613, USA.
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Shi
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Katsev
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Cai
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Evans
D029404:Activin Receptors; D000818:Animals; D015415:Biomarkers; D019485:Bone Morphogenetic Proteins / Q000502:physiology*; D004268:DNA-Binding Proteins / Q000235:genetics; D015536:Down-Regulation; D018507:Gene Expression Regulation, Developmental; D006321:Heart / Q000196:embryology*; D000072576:Homeobox Protein Nkx-2.5; D018398:Homeodomain Proteins / Q000235:genetics; D017403:In Situ Hybridization; D010641:Phenotype; D017346:Protein Serine-Threonine Kinases / Q000235:genetics; D015398:Signal Transduction / Q000502:physiology*; D051785:Smad Proteins; D015534:Trans-Activators / Q000235:genetics; D014157:Transcription Factors; D029867:Xenopus Proteins; D014982:Xenopus laevis / Q000196:embryology
D015415:Biomarkers; D019485:Bone Morphogenetic Proteins; D004268:DNA-Binding Proteins; D000072576:Homeobox Protein Nkx-2.5; D018398:Homeodomain Proteins; C092720:NKX2-5 protein, Xenopus; C095552:NKX2-5 protein, human; D051785:Smad Proteins; D015534:Trans-Activators; D014157:Transcription Factors; D029867:Xenopus Proteins; D017346:Protein Serine-Threonine Kinases; D029404:Activin Receptors