{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,25]],"date-time":"2026-01-25T13:05:13Z","timestamp":1769346313827,"version":"3.49.0"},"reference-count":49,"publisher":"The Company of Biologists","issue":"21","license":[{"start":{"date-parts":[[2000,11,1]],"date-time":"2000-11-01T00:00:00Z","timestamp":973036800000},"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":[[2000,11,1]]},"abstract":"<jats:title>ABSTRACT<\/jats:title><jats:p>The platelet-derived growth factor alpha-receptor (PDGFR\u03b1) plays a vital role in the development of vertebrate embryos, since mice lacking PDGFR\u03b1 die in mid-gestation. PDGFR\u03b1 is expressed in several types of migratory progenitor cells in the embryo including cranial neural crest cells, lung smooth muscle progenitors and oligodendrocyte progenitors. To study PDGFR\u03b1 gene regulation and function during development, we generated transgenic mice by pronuclear injection of a 380 kb yeast artificial chromosome (YAC) containing the human PDGFR\u03b1 gene. The YAC transgene was expressed in neural crest cells, rescued the profound craniofacial abnormalities and spina bifida observed in PDGFR\u03b1 knockout mice and prolonged survival until birth. The ultimate cause of death was respiratory failure due to a defect in lung growth, stemming from failure of the transgene to be expressed correctly in lung smooth muscle progenitors. However, the YAC transgene was expressed faithfully in oligodendrocyte progenitors, which was not previously observed with plasmid-based transgenes containing only upstream PDGFR\u03b1 control sequences. Our data illustrate the complexity of PDGFR\u03b1 genetic control, provide clues to the location of critical regulatory elements and reveal a requirement for PDGF signalling in prenatal lung growth, which is distinct from the known requirement in postnatal alveogenesis. In addition, we found that the YAC transgene did not prolong survival of Patch mutant mice, indicating that genetic defects outside the PDGFR\u03b1 locus contribute to the early embryonic lethality of Patch mice.<\/jats:p>","DOI":"10.1242\/dev.127.21.4519","type":"journal-article","created":{"date-parts":[[2021,4,26]],"date-time":"2021-04-26T04:20:52Z","timestamp":1619410852000},"page":"4519-4529","source":"Crossref","is-referenced-by-count":60,"title":["A human YAC transgene rescues craniofacial and neural tube development in<i>PDGFR<\/i>\u03b1 knockout mice and uncovers a role for PDGFR\u03b1 in prenatal lung growth"],"prefix":"10.1242","volume":"127","author":[{"given":"Tao","family":"Sun","sequence":"first","affiliation":[{"name":"University College London 1 Wolfson Institute for Biomedical Research and Department of Biology, The Cruciform Building , , Gower Street, London WC1E 6BT, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Damith","family":"Jayatilake","sequence":"additional","affiliation":[{"name":"University College London 1 Wolfson Institute for Biomedical Research and Department of Biology, The Cruciform Building , , Gower Street, London WC1E 6BT, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Gijs B.","family":"Afink","sequence":"additional","affiliation":[{"name":"2 Department of Genetics and Pathology, Rudbeck Laboratory, University Hospital, S-751 85 Uppsala, Sweden"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Paris","family":"Ataliotis","sequence":"additional","affiliation":[{"name":"3 Molecular Medicine Unit, Institute of Child Health, 30 Guilford Street, London WC1N 1EH, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Monica","family":"Nist\u00e9r","sequence":"additional","affiliation":[{"name":"2 Department of Genetics and Pathology, Rudbeck Laboratory, University Hospital, S-751 85 Uppsala, Sweden"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"William D.","family":"Richardson","sequence":"additional","affiliation":[{"name":"University College London 1 Wolfson Institute for Biomedical Research and Department of Biology, The Cruciform Building , , Gower Street, London WC1E 6BT, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hazel K.","family":"Smith","sequence":"additional","affiliation":[{"name":"University College London 1 Wolfson Institute for Biomedical Research and Department of Biology, The Cruciform Building , , Gower Street, London WC1E 6BT, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"237","published-online":{"date-parts":[[2000,11,1]]},"reference":[{"key":"2023030307382884600_","first-page":"1667","article-title":"Molecular cloning and functional characterization of the human platelet-derived growth factor alpha receptor gene promoter","volume":"10","author":"Afink","year":"1995","journal-title":"Oncogene"},{"key":"2023030307382884600_","doi-asserted-by":"publisher","first-page":"95","DOI":"10.1016\/S0074-7696(08)62359-1","article-title":"Distribution and functions of platelet-derived growth factors and their receptors during embryogenesis","volume":"172","author":"Ataliotis","year":"1997","journal-title":"Int. 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