Evidence for a role of Smad6 in chick cardiac development.
Bone morphogenetic proteins (BMPs), members of the transforming growth factor-beta (TGF-beta) superfamily, are obligatory growth factors for early embryogenesis and heart formation. SMAD proteins transduce signals of the TGF-beta superfamily. We isolated chicken Smad6 (cSmad6), a member of inhibitory SMADs, and found its expression to be remarkably restricted to the developing heart, eyes, and limbs. cSmad6 expression was detected in the cardiogenic region of stage 5 embryos and overlapped Nkx2-5 and bmp-2, -4, and -7 expression. Throughout development, cSmad6 was expressed strongly in the heart, primarily in the myocardium, endocardium, and endocardial cushion tissue. Myocardial expression of cSmad6 was stronger in the forming septum, where highly localized expression of bmp-2 and -4 was also observed. Ectopically applied BMP-2 protein induced the expression of cSmad6, a putative negative regulator of BMP-signaling pathway, in anterior medial mesoendoderm of stage 4-5 embryos. In addition, blocking of BMP signaling using Noggin downregulated cSmad6 in cardiogenic tissue. cSmad1, one of the positive mediators of BMP signaling, was also expressed in cardiogenic region, but was not BMP-2 inducible. Our data suggest that cSmad6 has a role in orchestrating BMP-mediated cardiac development. We propose the possible mechanism of action of cSmad6 as modulating BMP signal by keeping a balance between constitutively expressed pathway-specific cSmad1 and ligand-induced inhibitory cSmad6 in the developing heart.
Yamada
M
M
Department of Cell Biology, Baylor College of Medicine, Houston, Texas, 77030, USA.
Szendro
P I
PI
Prokscha
A
A
Schwartz
R J
RJ
Eichele
G
G
D000595:Amino Acid Sequence; D000818:Animals; D055396:Bone Morphogenetic Protein 2; D055415:Bone Morphogenetic Protein 4; D055419:Bone Morphogenetic Protein 7; D019485:Bone Morphogenetic Proteins / Q000235:genetics / Q000494:pharmacology; D002642:Chick Embryo; D004268:DNA-Binding Proteins / Q000737:chemistry / Q000235:genetics*; D004699:Endocardium / Q000378:metabolism; D005123:Eye / Q000196:embryology; D018507:Gene Expression Regulation, Developmental / Q000187:drug effects; D006321:Heart / Q000196:embryology*; D000072576:Homeobox Protein Nkx-2.5; D018398:Homeodomain Proteins / Q000235:genetics; D018878:Limb Buds / Q000502:physiology; D008969:Molecular Sequence Data; D009206:Myocardium / Q000378:metabolism; D009924:Organ Culture Techniques; D051381:Rats; D015183:Restriction Mapping; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction; D051905:Smad6 Protein; D015534:Trans-Activators / Q000737:chemistry / Q000235:genetics*; D014157:Transcription Factors; D016212:Transforming Growth Factor beta / Q000502:physiology; D029867:Xenopus Proteins
C525720:Bmp2 protein, rat; C525811:Bmp4 protein, rat; C525821:Bmp7 protein, rat; D055396:Bone Morphogenetic Protein 2; D055415:Bone Morphogenetic Protein 4; D055419:Bone Morphogenetic Protein 7; D019485:Bone Morphogenetic Proteins; D004268:DNA-Binding Proteins; D000072576:Homeobox Protein Nkx-2.5; D018398:Homeodomain Proteins; C095552:NKX2-5 protein, human; D051905:Smad6 Protein; D015534:Trans-Activators; D014157:Transcription Factors; D016212:Transforming Growth Factor beta; D029867:Xenopus Proteins; C525812:bmp4 protein, Xenopus; C525822:bmp7.1 protein, Xenopus