{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T02:14:50Z","timestamp":1790648090757,"version":"4.1.0"},"reference-count":48,"publisher":"The Company of Biologists","issue":"12","license":[{"start":{"date-parts":[[1996,12,1]],"date-time":"1996-12-01T00:00:00Z","timestamp":849398400000},"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":[[1996,12,1]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n               <jats:p>The mouse brachypodism locus encodes a bone morphogenetic protein (BMP)-like molecule called growth\/differentiation factor 5 (GDF5). Here we show that Gdf5 transcripts are expressed in a striking pattern of transverse stripes within many skeletal precursors in the developing limb. The number, location and time of appearance of these stripes corresponds to the sites where joints will later form between skeletal elements. Null mutations in Gdf5 disrupt the formation of more than 30% of the synovial joints in the limb, leading to complete or partial fusions between particular skeletal elements, and changes in the patterns of repeating structures in the digits, wrists and ankles. Mice carrying null mutations in both Gdf5 and another BMP family member, Bmp5, show additional abnormalities not observed in either of the single mutants. These defects include disruption of the sternebrae within the sternum and abnormal formation of the fibrocartilaginous joints between the sternebrae and ribs. Previous studies have shown that members of the BMP family are required for normal development of cartilage and bone. The current studies suggest that particular BMP family members may also play an essential role in the segmentation process that cleaves skeletal precursors into separate elements. This process helps determine the number of elements in repeating series in both limbs and sternum, and is required for normal generation of the functional articulations between many adjacent structures in the vertebrate skeleton.<\/jats:p>","DOI":"10.1242\/dev.122.12.3969","type":"journal-article","created":{"date-parts":[[2021,4,26]],"date-time":"2021-04-26T02:41:03Z","timestamp":1619404863000},"page":"3969-3979","source":"Crossref","is-referenced-by-count":342,"title":["Joint patterning defects caused by single and double mutations in members of the bone morphogenetic protein (BMP) family"],"prefix":"10.1242","volume":"122","author":[{"given":"Elaine E.","family":"Storm","sequence":"first","affiliation":[{"name":"Stanford University School of Medicine Department of Developmental Biology, Beckman Center B300 , , Stanford, CA 94305-5427, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David M.","family":"Kingsley","sequence":"additional","affiliation":[{"name":"Stanford University School of Medicine Department of Developmental Biology, Beckman Center B300 , , Stanford, CA 94305-5427, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"237","published-online":{"date-parts":[[1996,12,1]]},"reference":[{"key":"2025021323595823300_DEVELOP_122_12_3969C1","doi-asserted-by":"publisher","first-page":"28227","DOI":"10.1016\/S0021-9258(18)46918-9","article-title":"Cartilage-derived morphogenetic proteins. New members of the transforming growth factor-beta superfamily predominantly expressed in long bones during human embryonic development","volume":"269","author":"Chang","year":"1994","journal-title":"J. Biol.C hem."},{"key":"2025021323595823300_DEVELOP_122_12_3969C2","first-page":"373","article-title":"Studies on the morphogenesis of the mouse sternum. I. Normal embryonic development","volume":"86","author":"Chen","year":"1952","journal-title":"J. Anat., Lond."},{"key":"2025021323595823300_DEVELOP_122_12_3969C3","first-page":"387","article-title":"Studies on the morphogenesis of the mouse sternum. II Experiments on the origin of the sternum and its capacity for selfdifferentiation in vitro","volume":"86","author":"Chen","year":"1952","journal-title":"J. Anat., Lond."},{"key":"2025021323595823300_DEVELOP_122_12_3969C4","first-page":"132","article-title":"Studies on the morphogenesis of the mouse sternum. III. Experiments on the closure and segmentation of sternal bands","volume":"87","author":"Chen","year":"1953","journal-title":"J. Anat., Lond."},{"key":"2025021323595823300_DEVELOP_122_12_3969C5","doi-asserted-by":"publisher","first-page":"383","DOI":"10.1242\/dev.99.3.383","article-title":"The spatial and temporal pattern of collagens I and II and keratan sulphate in the developing chick metatarsophalangeal joint","volume":"99","author":"Craig","year":"1987","journal-title":"Development"},{"key":"2025021323595823300_DEVELOP_122_12_3969C6","volume-title":"Development of the Limbs of the Mouse. Stanford University Ph.D. Thesis","author":"Dalgleish","year":"1964"},{"key":"2025021323595823300_DEVELOP_122_12_3969C7","doi-asserted-by":"publisher","first-page":"401","DOI":"10.1016\/0012-1606(66)90022-4","article-title":"The role of movement in embryonic joint development","volume":"14","author":"Drachman","year":"1966","journal-title":"Dev. Biol."},{"key":"2025021323595823300_DEVELOP_122_12_3969C8","first-page":"371","article-title":"In vitro chondrogenesis of limb mesoderm from normal and brachypod mouse embryos","volume":"33","author":"Elmer","year":"1975","journal-title":"J. Embryol. Exp. Morph."},{"key":"2025021323595823300_DEVELOP_122_12_3969C9","first-page":"316","article-title":"Experiments on the development in vitro of the avian knee-joint","volume":"116","author":"Fell","year":"1934","journal-title":"Proc. Royal Soc. B"},{"key":"2025021323595823300_DEVELOP_122_12_3969C10","doi-asserted-by":"publisher","first-page":"684","DOI":"10.1038\/372684a0","article-title":"The signalling molecule BMP4 mediates apoptosis in the rhombencephalic neural crest","volume":"372","author":"Graham","year":"1994","journal-title":"Nature"},{"key":"2025021323595823300_DEVELOP_122_12_3969C11","volume-title":"Anatomy, Descriptive and Surgical","author":"Gray","year":"1901"},{"key":"2025021323595823300_DEVELOP_122_12_3969C12","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1002\/jmor.1050880102","article-title":"Further morphological effects of the short ear gene in the house mouse","volume":"88","author":"Green","year":"1951","journal-title":"J. Morphol."},{"key":"2025021323595823300_DEVELOP_122_12_3969C13","doi-asserted-by":"publisher","first-page":"129","DOI":"10.1002\/jez.1401670202","article-title":"Mechanism of the pleiotropic effects of the short ear mutant gene in the mouse","volume":"167","author":"Green","year":"1968","journal-title":"J. Exp. Zool."},{"key":"2025021323595823300_DEVELOP_122_12_3969C14","first-page":"119","article-title":"The anatomy and development of brachypodism in the mouse","volume":"30","author":"Gr\u00fcneberg","year":"1973","journal-title":"J. Embryol. Exp. Morph."},{"key":"2025021323595823300_DEVELOP_122_12_3969C15","first-page":"3","article-title":"The development of joints","volume":"81","author":"Haines","year":"1947","journal-title":"J. Anat."},{"key":"2025021323595823300_DEVELOP_122_12_3969C16","doi-asserted-by":"publisher","first-page":"107","DOI":"10.1007\/BF00174948","article-title":"The membranous skeleton: the role of cell condensations in vertebrate skeletogenesis","volume":"186","author":"Hall","year":"1992","journal-title":"Anat. Embryol."},{"key":"2025021323595823300_DEVELOP_122_12_3969C17","first-page":"S163","article-title":"In situ localization and in vitro activity of BMP-13","volume":"10","author":"Hattersley","year":"1995","journal-title":"J. Bone Min. Res."},{"key":"2025021323595823300_DEVELOP_122_12_3969C18","volume-title":"The Development of the Vertebrate Limb. Oxford: Clarendon Press","author":"Hinchliffe","year":"1980"},{"key":"2025021323595823300_DEVELOP_122_12_3969C19","doi-asserted-by":"publisher","first-page":"1580","DOI":"10.1101\/gad.10.13.1580","article-title":"Bone morphogenetic proteins: multifunctional regulators of vertebrate development","volume":"10","author":"Hogan","year":"1996","journal-title":"Genes Dev."},{"key":"2025021323595823300_DEVELOP_122_12_3969C20","first-page":"115","article-title":"An experimental investigation into the early development of the chick elbow joint","volume":"39","author":"Holder","year":"1977","journal-title":"J. Embryol. Exp. Morph."},{"key":"2025021323595823300_DEVELOP_122_12_3969C21","doi-asserted-by":"publisher","first-page":"112","DOI":"10.1006\/dbio.1994.1300","article-title":"BMP5 and the molecular, skeletal, and soft-tissue alterations in short ear mice","volume":"166","author":"King","year":"1994","journal-title":"Dev. Biol."},{"key":"2025021323595823300_DEVELOP_122_12_3969C22","doi-asserted-by":"publisher","first-page":"70","DOI":"10.1111\/j.1749-6632.1996.tb56245.x","article-title":"The role of BMPs and GDFs in development of region-specific skeletal structures","volume":"785","author":"King","year":"1996","journal-title":"Annals New York Acad. Sci. USA"},{"key":"2025021323595823300_DEVELOP_122_12_3969C23","doi-asserted-by":"publisher","first-page":"133","DOI":"10.1101\/gad.8.2.133","article-title":"The TGF-beta superfamily: new members, new receptors, and new genetic tests of function in different organisms","volume":"8","author":"Kingsley","year":"1994","journal-title":"Genes Dev."},{"key":"2025021323595823300_DEVELOP_122_12_3969C24","doi-asserted-by":"publisher","first-page":"16","DOI":"10.1016\/0168-9525(94)90014-0","article-title":"What do BMPs do in mammals? Clues from the mouse short ear mutation","volume":"10","author":"Kingsley","year":"1994","journal-title":"Trends Genet."},{"key":"2025021323595823300_DEVELOP_122_12_3969C25","doi-asserted-by":"publisher","first-page":"399","DOI":"10.1016\/0092-8674(92)90510-J","article-title":"The mouse short ear skeletal morphogenesis locus is associated with defects in a bone morphogenetic member of the TGF-\u03b2 superfamily","volume":"71","author":"Kingsley","year":"1992","journal-title":"Cell"},{"key":"2025021323595823300_DEVELOP_122_12_3969C26","doi-asserted-by":"publisher","first-page":"293","DOI":"10.1093\/oxfordjournals.jhered.a106335","article-title":"Brachypodism, a recessive mutation of house mice","volume":"43","author":"Landauer","year":"1952","journal-title":"J. Heredity"},{"key":"2025021323595823300_DEVELOP_122_12_3969C27","doi-asserted-by":"publisher","first-page":"323","DOI":"10.1007\/BF00283684","article-title":"A severe autosomal recessive acromesomelic dysplasia, the Hunter-Thompson type, and comparison with the Grebe type","volume":"81","author":"Langer","year":"1989","journal-title":"Hum. Genet."},{"key":"2025021323595823300_DEVELOP_122_12_3969C28","doi-asserted-by":"publisher","first-page":"41","DOI":"10.1002\/tera.1420520106","article-title":"Clusterin expression during programmed and teratogen-induced cell death in the postimplantation rat embryo","volume":"52","author":"Little","year":"1995","journal-title":"Teratology"},{"key":"2025021323595823300_DEVELOP_122_12_3969C29","doi-asserted-by":"publisher","first-page":"835","DOI":"10.1038\/359835a0","article-title":"Homeotic transformation of the occipital bones of the skull by ectopic expression of a homeobox gene","volume":"359","author":"Lufkin","year":"1992","journal-title":"Nature"},{"key":"2025021323595823300_DEVELOP_122_12_3969C30","doi-asserted-by":"publisher","first-page":"1657","DOI":"10.1101\/gad.3.11.1657","article-title":"Patterns of expression of murine Vgr-1 and BMP-2a RNA suggest that transforming growth factor-beta-like genes coordinately regulate aspects of embryonic development","volume":"3","author":"Lyons","year":"1989","journal-title":"Genes Dev."},{"key":"2025021323595823300_DEVELOP_122_12_3969C31","first-page":"445","article-title":"Long bone geometry and strength in adult BMP-5 deficient mice","volume":"16","author":"Mikic","year":"1995","journal-title":"Bone"},{"key":"2025021323595823300_DEVELOP_122_12_3969C32","article-title":"Mechanical and geometric changes in the growing femora of BMP-5 deficient mice","volume-title":"Bone (in press)","author":"Mikic","year":"1996"},{"key":"2025021323595823300_DEVELOP_122_12_3969C33","first-page":"1","article-title":"\u00c9tude morphog\u00e9n\u00e9tique de trois malformations cong\u00e9nitales de l\u2019autopode chez la souris (syndactylisme \u2013 brachypodisme \u2013 H\u00e9mim\u00e9lie dominante) par des m\u00e9thodes cytochimiques","volume":"16","author":"Milaire","year":"1965","journal-title":"Acad\u00e9mie Royale de Belgique, Classe de Science. M\u00e9moires"},{"key":"2025021323595823300_DEVELOP_122_12_3969C34","doi-asserted-by":"publisher","first-page":"475","DOI":"10.1002\/aja.1001510403","article-title":"Development of the diarthrodial joints in the rat embryo","volume":"151","author":"Mitrovic","year":"1978","journal-title":"Am. J. Anat."},{"key":"2025021323595823300_DEVELOP_122_12_3969C35","first-page":"835","article-title":"Defects in the growth plate of brachypodism in mice--light and electron microscopic findings and cell proliferation by the method of tritiated thymidine autoradiography","volume":"58","author":"Nakamura","year":"1984","journal-title":"Nippon Seikeigeka Gakkai Zasshi"},{"key":"2025021323595823300_DEVELOP_122_12_3969C36","doi-asserted-by":"publisher","first-page":"352","DOI":"10.1002\/aja.1002030307","article-title":"Collagen gene expression during development of avian synovial joints: transient expression of types II and XI collagen genes in the joint capsule","volume":"203","author":"Nalin","year":"1995","journal-title":"Dev. Dynamics"},{"key":"2025021323595823300_DEVELOP_122_12_3969C37","doi-asserted-by":"publisher","first-page":"862","DOI":"10.2307\/2408905","article-title":"Evolution and morphogenetic rules: the shape of the vertebrate limb in ontogeny and phylogeny","volume":"42","author":"Oster","year":"1988","journal-title":"Evolution"},{"key":"2025021323595823300_DEVELOP_122_12_3969C38","volume-title":"On the Structure and Development of the Shoulder-girdle and Sternum in the Vertebrata. Piccadilly: Robert Hardwicke","author":"Parker","year":"1867"},{"key":"2025021323595823300_DEVELOP_122_12_3969C39","doi-asserted-by":"publisher","first-page":"1601","DOI":"10.1073\/pnas.69.6.1601","article-title":"Biochemical sequences in the transformation of normal fibroblasts in adolescent rats","volume":"69","author":"Reddi","year":"1972","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"2025021323595823300_DEVELOP_122_12_3969C40","doi-asserted-by":"publisher","first-page":"97","DOI":"10.1016\/0168-9525(92)90063-A","article-title":"The BMP proteins in bone formation and repair","volume":"8","author":"Rosen","year":"1992","journal-title":"Trends Genet"},{"key":"2025021323595823300_DEVELOP_122_12_3969C41","doi-asserted-by":"publisher","first-page":"431","DOI":"10.1007\/BF00267823","article-title":"A single protocol to detect transcripts of various types and expression levels in neural tissue and cultured cells: in situ hybridization using digoxigenin-labelled cRNA probes","volume":"100","author":"Schaeren-Wiemers","year":"1993","journal-title":"Histochemistry"},{"key":"2025021323595823300_DEVELOP_122_12_3969C42","first-page":"319","article-title":"A morphogenetic approach to the origin and basic organization of the tetrapod limb","volume":"20","author":"Shubin","year":"1986","journal-title":"Evolutionary Biol."},{"key":"2025021323595823300_DEVELOP_122_12_3969C43","doi-asserted-by":"publisher","first-page":"639","DOI":"10.1038\/368639a0","article-title":"Limb alterations in brachypodism mice due to mutations in a new member of the TGF-beta superfamily","volume":"368","author":"Storm","year":"1994","journal-title":"Nature"},{"key":"2025021323595823300_DEVELOP_122_12_3969C44","doi-asserted-by":"crossref","DOI":"10.1038\/ng0396-315","article-title":"A human chondrodysplasia due to a mutation in a TGF-B superfamily member","volume-title":"Nature Genet.","author":"Thomas","year":"1996"},{"key":"2025021323595823300_DEVELOP_122_12_3969C45","doi-asserted-by":"publisher","first-page":"893","DOI":"10.1126\/science.150.3698.893","article-title":"Bone. Formation by autoinduction","volume":"150","author":"Urist","year":"1965","journal-title":"Science"},{"key":"2025021323595823300_DEVELOP_122_12_3969C46","doi-asserted-by":"publisher","first-page":"41","DOI":"10.1002\/jez.1402490109","article-title":"A staging system for mouse limb development","volume":"249","author":"Wanek","year":"1989","journal-title":"J. Exp. Zool."},{"key":"2025021323595823300_DEVELOP_122_12_3969C47","first-page":"S148","article-title":"Preliminary characterization of the biological activities of rhBMP-12","volume":"10","author":"Wolfman","year":"1995","journal-title":"J. Bone Min. Res."},{"key":"2025021323595823300_DEVELOP_122_12_3969C48","doi-asserted-by":"publisher","first-page":"738","DOI":"10.1126\/science.272.5262.738","article-title":"Requirement for BMP signaling in interdigital apoptosis and scale formation","volume":"272","author":"Zou","year":"1996","journal-title":"Science"}],"container-title":["Development"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/journals.biologists.com\/dev\/article-pdf\/122\/12\/3969\/3122579\/develop_122_12_3969.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/journals.biologists.com\/dev\/article-pdf\/122\/12\/3969\/3122579\/develop_122_12_3969.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,2,14]],"date-time":"2025-02-14T00:00:30Z","timestamp":1739491230000},"score":1,"resource":{"primary":{"URL":"https:\/\/journals.biologists.com\/dev\/article\/122\/12\/3969\/39130\/Joint-patterning-defects-caused-by-single-and"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[1996,12,1]]},"references-count":48,"journal-issue":{"issue":"12","published-print":{"date-parts":[[1996,12,1]]}},"URL":"https:\/\/doi.org\/10.1242\/dev.122.12.3969","relation":{},"ISSN":["0950-1991","1477-9129"],"issn-type":[{"value":"0950-1991","type":"print"},{"value":"1477-9129","type":"electronic"}],"subject":[],"published":{"date-parts":[[1996,12,1]]}}}