{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T06:07:07Z","timestamp":1791266827919,"version":"4.1.0"},"reference-count":33,"publisher":"American Association for the Advancement of Science (AAAS)","issue":"5677","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Science"],"published-print":{"date-parts":[[2004,6,11]]},"abstract":"<jats:p>\n            Anterior-to-posterior patterning, the process whereby our digits are differently shaped, is a key aspect of limb development. It depends on the localized expression in posterior limb bud of\n            <jats:italic>Sonic hedgehog<\/jats:italic>\n            (\n            <jats:italic>Shh<\/jats:italic>\n            ) and the morphogenetic potential of its diffusing product. By using an inversion of and a large deficiency in the mouse\n            <jats:italic>HoxD<\/jats:italic>\n            cluster, we found that a perturbation in the early collinear expression of\n            <jats:italic>Hoxd11, Hoxd12<\/jats:italic>\n            , and\n            <jats:italic>Hoxd13<\/jats:italic>\n            in limb buds led to a loss of asymmetry. Ectopic\n            <jats:italic>Hox<\/jats:italic>\n            gene expression triggered abnormal\n            <jats:italic>Shh<\/jats:italic>\n            transcription, which in turn induced symmetrical expression of\n            <jats:italic>Hox<\/jats:italic>\n            genes in digits, thereby generating double posterior limbs. We conclude that early posterior restriction of\n            <jats:italic>Hox<\/jats:italic>\n            gene products sets up an anterior-posterior prepattern, which determines the localized activation of\n            <jats:italic>Shh<\/jats:italic>\n            . This signal is subsequently translated into digit morphological asymmetry by promoting the late expression of\n            <jats:italic>Hoxd<\/jats:italic>\n            genes, two collinear processes relying on opposite genomic topographies, upstream and downstream\n            <jats:italic>Shh<\/jats:italic>\n            signaling.\n          <\/jats:p>","DOI":"10.1126\/science.1096049","type":"journal-article","created":{"date-parts":[[2004,6,10]],"date-time":"2004-06-10T19:53:06Z","timestamp":1086897186000},"page":"1669-1672","source":"Crossref","is-referenced-by-count":251,"title":["A Dual Role for\n            <i>Hox<\/i>\n            Genes in Limb Anterior-Posterior Asymmetry"],"prefix":"10.1126","volume":"304","author":[{"given":"Jo\u0301zsef","family":"Za\u0301ka\u0301ny","sequence":"first","affiliation":[{"name":"Department of Zoology and Animal Biology and National Program Frontiers in Genetics, University of Geneva, Sciences III, Quai Ernest Ansermet 30, 1211 Geneva 4, Switzerland."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marie","family":"Kmita","sequence":"additional","affiliation":[{"name":"Department of Zoology and Animal Biology and National Program Frontiers in Genetics, University of Geneva, Sciences III, Quai Ernest Ansermet 30, 1211 Geneva 4, Switzerland."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Denis","family":"Duboule","sequence":"additional","affiliation":[{"name":"Department of Zoology and Animal Biology and National Program Frontiers in Genetics, University of Geneva, Sciences III, Quai Ernest Ansermet 30, 1211 Geneva 4, Switzerland."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"221","reference":[{"key":"e_1_3_1_2_2","first-page":"847","volume":"46","year":"2002","unstructured":"C. Tickle, Int. J. Dev. Biol.46, 847 (2002).","journal-title":"Int. J. Dev. Biol."},{"key":"e_1_3_1_3_2","doi-asserted-by":"publisher","DOI":"10.1016\/0092-8674(93)90626-2"},{"key":"e_1_3_1_4_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1830500100"},{"key":"e_1_3_1_5_2","doi-asserted-by":"publisher","DOI":"10.1242\/dev.127.7.1337"},{"key":"e_1_3_1_6_2","doi-asserted-by":"publisher","DOI":"10.1242\/dev.00245"},{"key":"e_1_3_1_7_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0925-4773(00)00492-5"},{"key":"e_1_3_1_8_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0960-9822(99)80022-0"},{"key":"e_1_3_1_9_2","doi-asserted-by":"publisher","DOI":"10.1101\/gad.9.13.1645"},{"key":"e_1_3_1_10_2","doi-asserted-by":"publisher","DOI":"10.1242\/dev.126.21.4817"},{"key":"e_1_3_1_11_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0092-8674(00)80678-9"},{"key":"e_1_3_1_12_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.1075620"},{"key":"e_1_3_1_13_2","doi-asserted-by":"publisher","DOI":"10.1038\/nature01033"},{"key":"e_1_3_1_14_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0092-8674(03)00310-6"},{"key":"e_1_3_1_15_2","doi-asserted-by":"publisher","DOI":"10.1038\/nature01189"},{"key":"e_1_3_1_16_2","doi-asserted-by":"publisher","DOI":"10.1101\/gad.219202"},{"key":"e_1_3_1_17_2","doi-asserted-by":"publisher","DOI":"10.1242\/dev.127.11.2461"},{"key":"e_1_3_1_18_2","doi-asserted-by":"publisher","DOI":"10.1242\/dev.127.10.2133"},{"key":"e_1_3_1_19_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0925-4773(97)00656-4"},{"key":"e_1_3_1_20_2","doi-asserted-by":"publisher","DOI":"10.1038\/342767a0"},{"key":"e_1_3_1_21_2","doi-asserted-by":"publisher","DOI":"10.1006\/dbio.1993.1145"},{"key":"e_1_3_1_22_2","doi-asserted-by":"publisher","DOI":"10.1242\/dev.122.5.1449"},{"key":"e_1_3_1_23_2","doi-asserted-by":"publisher","DOI":"10.1242\/dev.122.12.3851"},{"key":"e_1_3_1_24_2","doi-asserted-by":"publisher","DOI":"10.1016\/0092-8674(94)90524-X"},{"key":"e_1_3_1_25_2","doi-asserted-by":"publisher","DOI":"10.1242\/dev.124.22.4523"},{"key":"e_1_3_1_26_2","doi-asserted-by":"publisher","DOI":"10.1007\/s004410051263"},{"key":"e_1_3_1_27_2","doi-asserted-by":"publisher","DOI":"10.1242\/dev.126.1.13"},{"key":"e_1_3_1_28_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0092-8674(00)81303-3"},{"key":"e_1_3_1_29_2","doi-asserted-by":"publisher","DOI":"10.1002\/(SICI)1098-2795(199811)51:3<274::AID-MRD6>3.0.CO;2-M"},{"key":"e_1_3_1_30_2","doi-asserted-by":"publisher","DOI":"10.1038\/3861"},{"key":"e_1_3_1_31_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0092-8674(01)00436-6"},{"key":"e_1_3_1_32_2","doi-asserted-by":"publisher","DOI":"10.1093\/emboj\/16.14.4393"},{"key":"e_1_3_1_33_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0092-8674(01)00369-5"},{"key":"e_1_3_1_34_2","unstructured":"We thank M. Friedli and N. Fraudeau for technical assistance; J. Deschamps C. Tabin J. Cobb and P. Vassalli for comments; and J. Deschamps A. Zuniga D. Srivastava and A. McMahon for probes. This work was supported by funds from the Canton de Gen\u00e8ve the Swiss National Research Fund the Claraz and Louis-Jeantet foundations and European Union grants \u201cEumorphia\u201d and \u201cCells into Organs.\u201d"}],"container-title":["Science"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.science.org\/doi\/pdf\/10.1126\/science.1096049","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,1,10]],"date-time":"2024-01-10T04:14:02Z","timestamp":1704860042000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.science.org\/doi\/10.1126\/science.1096049"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2004,6,11]]},"references-count":33,"journal-issue":{"issue":"5677","published-print":{"date-parts":[[2004,6,11]]}},"alternative-id":["10.1126\/science.1096049"],"URL":"https:\/\/doi.org\/10.1126\/science.1096049","relation":{},"ISSN":["0036-8075","1095-9203"],"issn-type":[{"value":"0036-8075","type":"print"},{"value":"1095-9203","type":"electronic"}],"subject":[],"published":{"date-parts":[[2004,6,11]]}}}