{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,3]],"date-time":"2026-10-03T23:28:44Z","timestamp":1791070124088,"version":"4.1.0"},"reference-count":51,"publisher":"The Company of Biologists","issue":"5","license":[{"start":{"date-parts":[[1998,3,1]],"date-time":"1998-03-01T00:00:00Z","timestamp":888710400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/www.biologists.com\/user-licence-1-1\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[1998,3,1]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n               <jats:p>Bone morphogenetic proteins (BMPs) participate in the development of nearly all organs and tissues. BMP signaling is mediated by specific Smad proteins, Smad1 and\/or Smad5, which undergo serine phosphorylation in response to BMP-receptor activation and are then translocated to the nucleus where they modulate transcription of target genes. We have identified a distantly related member of the Xenopus Smad family, Smad8, which lacks the C-terminal SSXS phosphorylation motif present in other Smads, and which appears to function in the BMP signaling pathway. During embryonic development, the spatial pattern of expression of Smad8 mirrors that of BMP-4. We show that an intact BMP signaling pathway is required for its expression. Overexpression of Smad8 in Xenopus embryos phenocopies the effect of blocking BMP- 4 signaling, leading to induction of a secondary axis on the ventral side of intact embryos and to direct neural induction in ectodermal explants. Furthermore, Smad8 can block BMP-4-mediated induction of ventral mesoderm- specific gene expression in ectodermal explants. Overexpression of Smad8 within dorsal cells, however, causes patterning defects that are distinct from those reported in BMP-4-deficient embryos, suggesting that Smad8 may interact with additional signaling pathways. Indeed, overexpression of Smad8 blocks expression of Xbra in whole animals, and partially blocks activin signaling in animal caps. In addition, Smad8 inhibits involution of mesodermal cells during gastrulation, a phenotype that is not observed following blockade of activin or BMPs in Xenopus. Together, these results are consistent with the hypothesis that Smad8 participates in a negative feedback loop in which BMP signaling induces the expression of Smad8, which then functions to negatively modulate the amplitude or duration of signaling downstream of BMPs and, possibly, downstream of other transforming growth factor-\u03b2 (TGF-\u03b2) family ligands.<\/jats:p>","DOI":"10.1242\/dev.125.5.857","type":"journal-article","created":{"date-parts":[[2021,4,26]],"date-time":"2021-04-26T03:33:43Z","timestamp":1619408023000},"page":"857-867","source":"Crossref","is-referenced-by-count":118,"title":["<i>Xenopus<\/i> Smad8 acts downstream of BMP-4 to modulate its activity during vertebrate embryonic patterning"],"prefix":"10.1242","volume":"125","author":[{"given":"Takuya","family":"Nakayama","sequence":"first","affiliation":[{"name":"Oregon Health Sciences University 1 Department of Cell and Developmental Biology, L215 , , School of Medicine, 3181 SW Sam Jackson Park Road, Portland, OR 97201-3098, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mark A.","family":"Snyder","sequence":"additional","affiliation":[{"name":"Oregon Health Sciences University 1 Department of Cell and Developmental Biology, L215 , , School of Medicine, 3181 SW Sam Jackson Park Road, Portland, OR 97201-3098, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Savraj S.","family":"Grewal","sequence":"additional","affiliation":[{"name":"Oregon Health Sciences University 1 Department of Cell and Developmental Biology, L215 , , School of Medicine, 3181 SW Sam Jackson Park Road, Portland, OR 97201-3098, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kazuhide","family":"Tsuneizumi","sequence":"additional","affiliation":[{"name":"The University of Tokyo 2 Institute of Molecular and Cellular Biosciences , , Yayoi 1-1-1, Tokyo 113, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tetsuya","family":"Tabata","sequence":"additional","affiliation":[{"name":"The University of Tokyo 2 Institute of Molecular and Cellular Biosciences , , Yayoi 1-1-1, Tokyo 113, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jan L.","family":"Christian","sequence":"additional","affiliation":[{"name":"Oregon Health Sciences University 1 Department of Cell and Developmental Biology, L215 , , School of Medicine, 3181 SW Sam Jackson Park Road, Portland, OR 97201-3098, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"237","published-online":{"date-parts":[[1998,3,1]]},"reference":[{"key":"2025021500502094900_DEVELOP_125_5_857C1","doi-asserted-by":"publisher","first-page":"681","DOI":"10.1242\/dev.115.3.681","article-title":"Ventral ectoderm of Xenopus forms neural tissue, including hindbrain, in response to activin","volume":"115","author":"Bolce","year":"1992","journal-title":"Development"},{"key":"2025021500502094900_DEVELOP_125_5_857C2","doi-asserted-by":"publisher","first-page":"13","DOI":"10.1101\/gad.7.1.13","article-title":"Interactions between Xwnt-8 and Spemann organizer signaling pathways generate dorsoventral pattern in the embryonic mesoderm of Xenopus","volume":"7","author":"Christian","year":"1993","journal-title":"Genes Dev."},{"key":"2025021500502094900_DEVELOP_125_5_857C3","doi-asserted-by":"publisher","first-page":"2177","DOI":"10.1242\/dev.121.7.2177","article-title":"Xwnt-8b: a maternally expressed Xenopus Wnt gene with a potential role in establishing the dorsoventral axis","volume":"121","author":"Cui","year":"1995","journal-title":"Development"},{"key":"2025021500502094900_DEVELOP_125_5_857C4","doi-asserted-by":"publisher","first-page":"22","DOI":"10.1006\/dbio.1996.0281","article-title":"Synergistic effects of Vg1 and Wnt signals in the specification of dorsal mesoderm and endoderm","volume":"180","author":"Cui","year":"1996","journal-title":"Dev. 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