{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,21]],"date-time":"2026-09-21T15:22:53Z","timestamp":1790004173620,"version":"4.0.1"},"reference-count":30,"publisher":"American Association for the Advancement of Science (AAAS)","issue":"5594","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Science"],"published-print":{"date-parts":[[2002,10,25]]},"abstract":"<jats:p>\n            Distal limb development and specification of digit identities in tetrapods are under the control of a mesenchymal organizer called the polarizing region.\n            <jats:italic>Sonic Hedgehog<\/jats:italic>\n            (SHH) is the morphogenetic signal produced by the polarizing region in the posterior limb bud. Ectopic anterior SHH signaling induces digit duplications and has been suspected as a major cause underlying congenital malformations that result in digit polydactyly. Here, we report that the polydactyly of\n            <jats:italic>Gli3<\/jats:italic>\n            -deficient mice arises independently of SHH signaling. Disruption of one or both\n            <jats:italic>Gli3<\/jats:italic>\n            alleles in mouse embryos lacking\n            <jats:italic>Shh<\/jats:italic>\n            progressively restores limb distal development and digit formation. Our genetic analysis indicates that SHH signaling counteracts GLI3-mediated repression of key regulator genes, cell survival, and distal progression of limb bud development.\n          <\/jats:p>","DOI":"10.1126\/science.1075620","type":"journal-article","created":{"date-parts":[[2002,10,24]],"date-time":"2002-10-24T21:03:20Z","timestamp":1035493400000},"page":"827-830","source":"Crossref","is-referenced-by-count":341,"title":["Progression of Vertebrate Limb Development Through SHH-Mediated Counteraction of GLI3"],"prefix":"10.1126","volume":"298","author":[{"given":"Pascal","family":"te Welscher","sequence":"first","affiliation":[{"name":"Department of Developmental Biology, Faculty of Biology, Utrecht University, Padualaan 8, NL-3584 CH Utrecht, Netherlands."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aime\u0301e","family":"Zuniga","sequence":"additional","affiliation":[{"name":"Department of Developmental Biology, Faculty of Biology, Utrecht University, Padualaan 8, NL-3584 CH Utrecht, Netherlands."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sanne","family":"Kuijper","sequence":"additional","affiliation":[{"name":"Hubrecht Laboratorium, Uppsalalaan 8, NL-3584 CT Utrecht, Netherlands."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thijs","family":"Drenth","sequence":"additional","affiliation":[{"name":"Department of Developmental Biology, Faculty of Biology, Utrecht University, Padualaan 8, NL-3584 CH Utrecht, Netherlands."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hans J.","family":"Goedemans","sequence":"additional","affiliation":[{"name":"Department of Developmental Biology, Faculty of Biology, Utrecht University, Padualaan 8, NL-3584 CH Utrecht, Netherlands."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Frits","family":"Meijlink","sequence":"additional","affiliation":[{"name":"Hubrecht Laboratorium, Uppsalalaan 8, NL-3584 CT Utrecht, Netherlands."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rolf","family":"Zeller","sequence":"additional","affiliation":[{"name":"Department of Developmental Biology, Faculty of Biology, Utrecht University, Padualaan 8, NL-3584 CH Utrecht, Netherlands."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"221","reference":[{"key":"e_1_3_1_2_2","doi-asserted-by":"publisher","DOI":"10.1101\/gad.938601"},{"key":"e_1_3_1_3_2","doi-asserted-by":"publisher","DOI":"10.1242\/dev.128.5.733"},{"key":"e_1_3_1_4_2","doi-asserted-by":"publisher","DOI":"10.1038\/ng0393-241"},{"key":"e_1_3_1_5_2","doi-asserted-by":"publisher","DOI":"10.1038\/383407a0"},{"key":"e_1_3_1_6_2","doi-asserted-by":"publisher","DOI":"10.1006\/dbio.2001.0346"},{"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":"10.1101\/gad.219202"},{"key":"e_1_3_1_9_2","doi-asserted-by":"publisher","DOI":"10.1242\/dev.126.1.13"},{"key":"e_1_3_1_10_2","doi-asserted-by":"publisher","DOI":"10.1038\/35023216"},{"key":"e_1_3_1_11_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0092-8674(00)80364-5"},{"key":"e_1_3_1_12_2","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.cellbio.17.1.87"},{"key":"e_1_3_1_13_2","doi-asserted-by":"publisher","DOI":"10.1038\/44157"},{"key":"e_1_3_1_14_2","doi-asserted-by":"publisher","DOI":"10.1101\/gad.9.13.1645"},{"key":"e_1_3_1_15_2","doi-asserted-by":"publisher","DOI":"10.1038\/ng1197-259"},{"key":"e_1_3_1_16_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0092-8674(00)80678-9"},{"key":"e_1_3_1_17_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.96.6.2880"},{"key":"e_1_3_1_18_2","doi-asserted-by":"crossref","unstructured":"A. Ruiz i Altaba Development 126 3205 (1999).","DOI":"10.1242\/dev.126.14.3205"},{"key":"e_1_3_1_19_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.274.12.8143"},{"key":"e_1_3_1_20_2","doi-asserted-by":"crossref","unstructured":"R. Brewster J. L. Mullor A. Ruiz i Altaba Development 127 4395 (2000).","DOI":"10.1242\/dev.127.20.4395"},{"key":"e_1_3_1_21_2","unstructured":"Shh \u2013\/\u2013 embryos the Lst J (inactivated Alx4 ) and Xt J (inactivated Gli3 ) mouse strains (superscript J indicates Jackson alleles) were used and genotyped as described ( 3 6 21 )."},{"key":"e_1_3_1_22_2","doi-asserted-by":"publisher","DOI":"10.1242\/dev.125.14.2711"},{"key":"e_1_3_1_23_2","doi-asserted-by":"publisher","DOI":"10.1006\/dbio.1999.9321"},{"key":"e_1_3_1_24_2","unstructured":"P. te Welscher et al. data not shown."},{"key":"e_1_3_1_25_2","doi-asserted-by":"publisher","DOI":"10.1016\/0959-437X(94)90069-F"},{"key":"e_1_3_1_26_2","doi-asserted-by":"publisher","DOI":"10.1007\/s004410051262"},{"key":"e_1_3_1_27_2","doi-asserted-by":"publisher","DOI":"10.1242\/dev.127.7.1337"},{"key":"e_1_3_1_28_2","doi-asserted-by":"publisher","DOI":"10.1038\/79916"},{"key":"e_1_3_1_29_2","unstructured":"Embryos were stained for cartilage and bones with the use of combined Alcian blue and Alizarin red coloring."},{"key":"e_1_3_1_30_2","unstructured":"Apoptotic cells were detected by incorporating fluorescein\u2013deoxyuridine 5\u2032-triphosphate into fragmented DNA using terminal transferase (Roche Diagnostics Mannheim Germany)."},{"key":"e_1_3_1_31_2","unstructured":"We thank J. Deschamps R. Dono G. Holl\u00e4nder R. Plasterk B. Scheres D. Welch and group members for comments and suggestions. A.Z. is a fellow of the Royal Netherlands Academy of Arts and Sciences. Supported by the Netherlands Research Organization (program grant 810.68.012\/3 to F.M. and R.Z.)."}],"container-title":["Science"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.science.org\/doi\/pdf\/10.1126\/science.1075620","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,1,10]],"date-time":"2024-01-10T03:22:25Z","timestamp":1704856945000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.science.org\/doi\/10.1126\/science.1075620"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2002,10,25]]},"references-count":30,"journal-issue":{"issue":"5594","published-print":{"date-parts":[[2002,10,25]]}},"alternative-id":["10.1126\/science.1075620"],"URL":"https:\/\/doi.org\/10.1126\/science.1075620","relation":{},"ISSN":["0036-8075","1095-9203"],"issn-type":[{"value":"0036-8075","type":"print"},{"value":"1095-9203","type":"electronic"}],"subject":[],"published":{"date-parts":[[2002,10,25]]}}}