{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,17]],"date-time":"2026-02-17T11:06:28Z","timestamp":1771326388958,"version":"3.50.1"},"reference-count":20,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2005,1,6]],"date-time":"2005-01-06T00:00:00Z","timestamp":1104969600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Developmental Dynamics"],"published-print":{"date-parts":[[2005,2]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>In most instances of preaxial polydactyly (PPD), <jats:italic>Sonic Hedgehog<\/jats:italic> (<jats:italic>Shh<\/jats:italic>), an essential limb patterning signal, is ectopically expressed in an anterior region of the developing limb in addition to the normal posterior domain. It is thought that this anterior <jats:italic>Shh<\/jats:italic> expression leads directly to the development of the extra digits. Recent reports have identified a conserved limb\u2010specific <jats:italic>Shh<\/jats:italic> enhancer \u223c1 megabase upstream of the <jats:italic>Shh<\/jats:italic> transcription initiation site, and individual base pair changes within this region are associated with PPD. We report here that a single base pair change within this enhancer is sufficient to drive \u03b2\u2010galactosidase expression in both anterior and posterior limb domains, similar to <jats:italic>Shh<\/jats:italic> expression in animal PPD models, whereas a wild\u2010type construct is expressed only in the posterior limb, similar to <jats:italic>Shh<\/jats:italic> expression in normal embryos. These findings provide the first direct evidence that a single base pair change within the limb\u2010specific <jats:italic>Shh<\/jats:italic> enhancer acts as a genetic basis for PPD. Developmental Dynamics 232:345\u2013348, 2005. \u00a9 2005 Wiley\u2010Liss, Inc.<\/jats:p>","DOI":"10.1002\/dvdy.20254","type":"journal-article","created":{"date-parts":[[2005,1,6]],"date-time":"2005-01-06T18:16:11Z","timestamp":1105035371000},"page":"345-348","source":"Crossref","is-referenced-by-count":51,"title":["Single base pair change in the long\u2010range <i>Sonic hedgehog<\/i> limb\u2010specific enhancer is a genetic basis for preaxial polydactyly"],"prefix":"10.1002","volume":"232","author":[{"given":"Sarah A.","family":"Maas","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"John F.","family":"Fallon","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2005,1,6]]},"reference":[{"key":"e_1_2_6_2_1","first-page":"969","article-title":"Unusual pattern of Sonic hedgehog expression in the polydactylous mouse mutant Hemimelic extra\u2010toes","volume":"46","author":"Blanc I","year":"2002","journal-title":"Int J Dev Biol"},{"key":"e_1_2_6_3_1","doi-asserted-by":"crossref","first-page":"2461","DOI":"10.1242\/dev.127.11.2461","article-title":"The bHLH transcription factor dHAND controls Sonic hedgehog expression and establishment of the zone of polarizing activity during limb development","volume":"127","author":"Charite J","year":"2000","journal-title":"Development"},{"key":"e_1_2_6_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/0092-8674(93)90627-3"},{"key":"e_1_2_6_5_1","doi-asserted-by":"crossref","first-page":"2213","DOI":"10.1242\/dev.120.8.2213","article-title":"Cis\u2010acting regulatory sequences governing Wnt\u20101 expression in the developing mouse CNS","volume":"120","author":"Echelard Y","year":"1994","journal-title":"Development"},{"key":"e_1_2_6_6_1","doi-asserted-by":"publisher","DOI":"10.1242\/dev.127.10.2133"},{"key":"e_1_2_6_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2004.07.024"},{"key":"e_1_2_6_8_1","doi-asserted-by":"crossref","first-page":"4523","DOI":"10.1242\/dev.124.22.4523","article-title":"Hoxd\u201012 differentially affects preaxial and postaxial chondrogenic branches in the limb and regulates Sonic hedgehog in a positive feedback loop","volume":"124","author":"Knezevic V","year":"1997","journal-title":"Development"},{"key":"e_1_2_6_9_1","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/ddg180"},{"key":"e_1_2_6_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0960-9822(95)00156-4"},{"key":"e_1_2_6_11_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature01655"},{"key":"e_1_2_6_12_1","doi-asserted-by":"publisher","DOI":"10.1101\/gad.9.13.1645"},{"key":"e_1_2_6_13_1","doi-asserted-by":"publisher","DOI":"10.1006\/dbio.1996.8457"},{"key":"e_1_2_6_14_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrg1001"},{"key":"e_1_2_6_15_1","doi-asserted-by":"publisher","DOI":"10.1016\/0092-8674(93)90626-2"},{"key":"e_1_2_6_16_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00335-033-2317-5"},{"key":"e_1_2_6_17_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0960-9822(99)80022-0"},{"key":"e_1_2_6_18_1","doi-asserted-by":"publisher","DOI":"10.1101\/gad.219202"},{"key":"e_1_2_6_19_1","doi-asserted-by":"crossref","first-page":"449","DOI":"10.1016\/S1534-5807(03)00095-9","article-title":"Patterning systems\u2014from one end of the limb to the other","volume":"4","author":"Tickle C","year":"2003","journal-title":"Dev Cell"},{"key":"e_1_2_6_20_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.1096049"},{"key":"e_1_2_6_21_1","first-page":"32","article-title":"Clinical and genetic studies on 12 preaxial polydactyly families and refinement of the localisation of the gene responsible to a 1.9 cM region on chromosome 7q36","volume":"36","author":"Zguricas J","year":"1999","journal-title":"J Med Genet"}],"container-title":["Developmental Dynamics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1002%2Fdvdy.20254","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/anatomypubs.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/dvdy.20254","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,13]],"date-time":"2025-10-13T09:06:47Z","timestamp":1760346407000},"score":1,"resource":{"primary":{"URL":"https:\/\/anatomypubs.onlinelibrary.wiley.com\/doi\/10.1002\/dvdy.20254"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2005,1,6]]},"references-count":20,"journal-issue":{"issue":"2","published-print":{"date-parts":[[2005,2]]}},"alternative-id":["10.1002\/dvdy.20254"],"URL":"https:\/\/doi.org\/10.1002\/dvdy.20254","archive":["Portico"],"relation":{},"ISSN":["1058-8388","1097-0177"],"issn-type":[{"value":"1058-8388","type":"print"},{"value":"1097-0177","type":"electronic"}],"subject":[],"published":{"date-parts":[[2005,1,6]]}}}