{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T17:45:22Z","timestamp":1791308722164,"version":"4.3.1"},"reference-count":54,"publisher":"The Company of Biologists","issue":"6","license":[{"start":{"date-parts":[[1995,6,1]],"date-time":"1995-06-01T00:00:00Z","timestamp":801964800000},"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":[[1995,6,1]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n               <jats:p>Transforming growth factor \u03b21 (TGF\u03b21) is shown here to be required for yolk sac haematopoiesis and endothelial differentiation. Mice with a targeted mutation in the TGF\u03b21 gene were examined to determine the cause of prenatal lethality, which occurs in 50% of homozygous TGF\u03b21 null (TGF\u03b21\u2212\/\u2212) conceptions. 50% of TGF\u03b21\u2212\/\u2212 and 25% of TGF\u03b21+\/\u2212 conceptuses were found to die at around 10.5 dpc. The primary defects were restricted to extraembryonic tissues, namely the yolk sac vasculature and haematopoietic system. The embryos per se showed developmental retardation, oedema and necrosis, which were probably secondary to the extraembryonic lesions. The defect in vasculogenesis appeared to affect endothelial differentiation, rather than the initial appearance and outgrowth of endothelial cells. Initial differentiation of yolk sac mesoderm to endothelial cells occurred, but defective differentiation resulted in inadequate capillary tube formation, and weak vessels with reduced cellular adhesiveness. Defective haematopoiesis resulted in a reduced erythroid cell number within the yolk sac. Defective yolk sac vasculogenesis and haematopoiesis were present either together, or in isolation of each other. The phenotypes are consistent with the observation of abundant TGF\u03b21 gene expression in both endothelial and haematopoietic precursors. The data indicate that the primary effect of loss of TGF\u03b21 function in vivo is not increased haematopoietic or endothelial cell proliferation, which might have been expected by deletion of a negative growth regulator, but defective haematopoiesis and endothelial differentiation.<\/jats:p>","DOI":"10.1242\/dev.121.6.1845","type":"journal-article","created":{"date-parts":[[2021,4,26]],"date-time":"2021-04-26T02:19:00Z","timestamp":1619403540000},"page":"1845-1854","source":"Crossref","is-referenced-by-count":867,"title":["Defective haematopoiesis and vasculogenesis in transforming growth factor-\u03b21 knock out mice"],"prefix":"10.1242","volume":"121","author":[{"given":"Marion C.","family":"Dickson","sequence":"first","affiliation":[{"name":"University of Glasgow, Duncan Guthrie Institute 1 Department of Medical Genetics , , Yorkhill, Glasgow, G3 8SJ, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Julie S.","family":"Martin","sequence":"additional","affiliation":[{"name":"University of Glasgow, Duncan Guthrie Institute 1 Department of Medical Genetics , , Yorkhill, Glasgow, G3 8SJ, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Frances M.","family":"Cousins","sequence":"additional","affiliation":[{"name":"University of Glasgow, Duncan Guthrie Institute 1 Department of Medical Genetics , , Yorkhill, Glasgow, G3 8SJ, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ashok B.","family":"Kulkarni","sequence":"additional","affiliation":[{"name":"National Institute of Neurological Disorders and Stroke, National Institutes of Health 2 Developmental and Metabolic Neurology Branch , , Bethesda, Maryland, 20892, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stefan","family":"Karlsson","sequence":"additional","affiliation":[{"name":"National Institute of Neurological Disorders and Stroke, National Institutes of Health 2 Developmental and Metabolic Neurology Branch , , Bethesda, Maryland, 20892, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rosemary J.","family":"Akhurst","sequence":"additional","affiliation":[{"name":"University of Glasgow, Duncan Guthrie Institute 1 Department of Medical Genetics , , Yorkhill, Glasgow, G3 8SJ, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"237","published-online":{"date-parts":[[1995,6,1]]},"reference":[{"key":"2025011514115807600_DEVELOP_121_6_1845C1","doi-asserted-by":"publisher","first-page":"645","DOI":"10.1242\/dev.108.4.645","article-title":"TGF beta in murine morphogenetic processes: the early embryo and cardiogenesis","volume":"108","author":"Akhurst","year":"1990","journal-title":"Development"},{"key":"2025011514115807600_DEVELOP_121_6_1845C2","first-page":"97","article-title":"The transforming growth factor beta family in vertebrate embryogenesis","volume-title":"Growth Factors and Signal Transduction in Development","author":"Akhurst","year":"1994"},{"key":"2025011514115807600_DEVELOP_121_6_1845C3","first-page":"217","article-title":"Production of transgenic mice","volume-title":"Mammalian Development: A Practical Approach","author":"Allen","year":"1987"},{"key":"2025011514115807600_DEVELOP_121_6_1845C4","doi-asserted-by":"publisher","first-page":"118","DOI":"10.1002\/jcp.1041530116","article-title":"Differential modulation of vascular cell integrin and extracellular matrix expression in vitro by TGF-beta1 correlates with reciprocal effects on cell migration","volume":"153","author":"Basson","year":"1992","journal-title":"J. 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