{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,17]],"date-time":"2025-10-17T19:41:44Z","timestamp":1760730104979},"reference-count":34,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2009,11,19]],"date-time":"2009-11-19T00:00:00Z","timestamp":1258588800000},"content-version":"unspecified","delay-in-days":0,"URL":"http:\/\/www.springer.com\/tdm"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["BMC Musculoskelet Disord"],"published-print":{"date-parts":[[2009,12]]},"abstract":"<jats:title>Abstract<\/jats:title>\n          <jats:sec>\n            <jats:title>Background<\/jats:title>\n            <jats:p>Idiopathic congenital talipes equinovarus (ICTEV) is a congenital limb deformity. Based on extended transmission disequilibrium testing, <jats:italic>Gli-Kruppel family member 3<\/jats:italic> (<jats:italic>Gli3<\/jats:italic>) has been identified as a candidate gene for ICTEV. Here, we verify the role of <jats:italic>Gli3<\/jats:italic> in ICTEV development.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Methods<\/jats:title>\n            <jats:p>Using the rat ICTEV model, we analyzed the differences in <jats:italic>Gli3<\/jats:italic> expression levels between model rats and normal control rats. We used luciferase reporter gene assays and ChIP\/EMSA assays to analyze the regulatory elements of <jats:italic>Gli3<\/jats:italic>.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Results<\/jats:title>\n            <jats:p>\n              <jats:italic>Gli3<\/jats:italic> showed higher expression levels in ICTEV model rats compared to controls (P &lt; 0.05). We identified repressor and activator regions in the rat <jats:italic>Gli3<\/jats:italic> promoter. The <jats:italic>Gli3<\/jats:italic> promoter also contains two putative Hoxd13 binding sites. Using EMSA, the Hoxd13 binding site 2 was found to directly interact with Hoxd13 <jats:italic>in vitro<\/jats:italic>. ChIP assays of the Hoxd13-<jats:italic>Gli3<\/jats:italic> promoter complex from a developing limb confirmed that endogenous Hoxd13 interacts with this region <jats:italic>in vivo<\/jats:italic>.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Conclusion<\/jats:title>\n            <jats:p>Our findings suggest that <jats:italic>HoxD13<\/jats:italic> directly interacts with the promoter of <jats:italic>Gli3<\/jats:italic>. The increase of <jats:italic>Gli3<\/jats:italic> expression in ICTEV model animal might result from the low expression of <jats:italic>HoxD13<\/jats:italic>.<\/jats:p>\n          <\/jats:sec>","DOI":"10.1186\/1471-2474-10-142","type":"journal-article","created":{"date-parts":[[2009,11,19]],"date-time":"2009-11-19T19:44:53Z","timestamp":1258659893000},"update-policy":"http:\/\/dx.doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":10,"title":["The expression of Gli3, regulated by HOXD13, may play a role in idiopathic congenital talipes equinovarus"],"prefix":"10.1186","volume":"10","author":[{"given":"DongHua","family":"Cao","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"ChunLian","family":"Jin","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"MeiHong","family":"Ren","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"ChangKun","family":"Lin","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xuan","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ning","family":"Zhao","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2009,11,19]]},"reference":[{"key":"720_CR1","doi-asserted-by":"publisher","first-page":"39","DOI":"10.1097\/00003086-200208000-00007","volume":"401","author":"FMD Dietz","year":"2002","unstructured":"Dietz FMD: The genetics of idiopathic clubfoot. 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