Smad7 inhibits mesoderm formation and promotes neural cell fate in Xenopus embryos.
We report the isolation and characterization of a new inhibitory Smad in Xenopus, which we have designated as Xenopus Smad7. Smad7 is present at fairly constant levels throughout early development and at blastula stages enriched in the ventral side of the animal hemisphere. The induction of mesoderm by TGF-beta-like signals is mediated by receptor ALK-4 and we show that Smad7 blocks signaling of ALK-4 in a graded fashion: lower levels of Smad7 block activation of dorsal mesoderm genes and higher levels block all mesoderm genes expression. Smad7 is able to directly activate neural markers in explants in the absence of mesoderm or endoderm. This neural-inducing activity of Smad7 may be due to inhibition of BMP-4 signaling because Smad7 can also block BMP-4-mediated mesoderm induction. Thus, Smad7 acts as a potent inhibitor of mesoderm formation and also activates the default neural induction pathway.
Bhushan
A
A
Clayton Foundation Laboratories for Peptide Biology, Salk Institute, 10010 North Torrey Pines Road, La Jolla, California, 92037, USA. bhushan@salk.edu
Chen
Y
Y
Vale
W
W
D030201:Activin Receptors, Type I; D000595:Amino Acid Sequence; D000818:Animals; D055415:Bone Morphogenetic Protein 4; D019485:Bone Morphogenetic Proteins / Q000378:metabolism; D003001:Cloning, Molecular; D004268:DNA-Binding Proteins / Q000737:chemistry* / Q000502:physiology; D018507:Gene Expression Regulation, Developmental / Q000235:genetics; D006651:Histocytochemistry; D017403:In Situ Hybridization; D008648:Mesoderm / Q000502:physiology*; D008845:Microinjections; D008969:Molecular Sequence Data; D012333:RNA, Messenger / Q000378:metabolism; D017978:Receptors, Growth Factor / Q000378:metabolism; D016415:Sequence Alignment; D017422:Sequence Analysis, DNA; D015398:Signal Transduction / Q000502:physiology; D051906:Smad7 Protein; D015534:Trans-Activators / Q000737:chemistry* / Q000502:physiology; D014981:Xenopus / Q000196:embryology*; D029867:Xenopus Proteins
D055415:Bone Morphogenetic Protein 4; D019485:Bone Morphogenetic Proteins; D004268:DNA-Binding Proteins; D012333:RNA, Messenger; D017978:Receptors, Growth Factor; D051906:Smad7 Protein; C497809:Smad7 protein, Xenopus; D015534:Trans-Activators; D029867:Xenopus Proteins; C525812:bmp4 protein, Xenopus; D030201:Activin Receptors, Type I