{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,1]],"date-time":"2026-04-01T19:50:18Z","timestamp":1775073018826,"version":"3.50.1"},"reference-count":58,"publisher":"Wiley","issue":"8","license":[{"start":{"date-parts":[[2013,9,19]],"date-time":"2013-09-19T00:00:00Z","timestamp":1379548800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100001659","name":"Deutsche Forschungsgemeinschaft","doi-asserted-by":"crossref","award":["Gr373-21"],"award-info":[{"award-number":["Gr373-21"]}],"id":[{"id":"10.13039\/501100001659","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100001659","name":"Deutsche Forschungsgemeinschaft","doi-asserted-by":"crossref","award":["GRK 767"],"award-info":[{"award-number":["GRK 767"]}],"id":[{"id":"10.13039\/501100001659","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Dev Growth Differ"],"published-print":{"date-parts":[[2013,10]]},"abstract":"<jats:p>The zinc finger transcription factor Gli3 is an important mediator of <jats:styled-content style=\"fixed-case\">S<\/jats:styled-content>onic hedgehog (Shh) signaling. During early embryonic development <jats:italic>Gli3<\/jats:italic> participates in patterning and growth of the central nervous system, face, skeleton, limb, tooth and gut. Precise regulation of the temporal and spatial expression of <jats:italic>Gli3<\/jats:italic> is crucial for the proper specification of these structures in mammals and other vertebrates. Previously we reported a set of human intronic <jats:italic>ci<\/jats:italic>s\u2010regulators controlling almost the entire known repertoire of endogenous <jats:italic>Gli3<\/jats:italic> expression in mouse neural tube and limbs. However, the genetic underpinning of <jats:italic><jats:styled-content style=\"fixed-case\">GLI<\/jats:styled-content>3<\/jats:italic> expression in other embryonic domains such as craniofacial structures and internal organs remain elusive. Here we demonstrate in a transgenic mice assay the potential of a subset of human\/fish conserved non\u2010coding sequences (<jats:styled-content style=\"fixed-case\">CNE<\/jats:styled-content>s) residing within <jats:italic><jats:styled-content style=\"fixed-case\">GLI<\/jats:styled-content>3<\/jats:italic> intronic intervals to induce reporter gene expression at known regions of endogenous <jats:italic>Gli3<\/jats:italic> transcription in embryonic domains other than central nervous system (<jats:styled-content style=\"fixed-case\">CNS<\/jats:styled-content>) and limbs. Highly specific reporter expression was observed in craniofacial structures, eye, gut, and genitourinary system. Moreover, the comparison of expression patterns directed by these intronic <jats:italic>cis<\/jats:italic>\u2010acting regulatory elements in mouse and zebrafish embryos suggests that in accordance with sequence conservation, the target site specificity of a subset of these elements remains preserved among these two lineages. Taken together with our recent investigations, it is proposed here that during vertebrate evolution the <jats:italic>Gli3<\/jats:italic> expression control acquired multiple, independently acting, intronic enhancers for spatiotemporal patterning of <jats:styled-content style=\"fixed-case\">CNS<\/jats:styled-content>, limbs, craniofacial structures and internal organs.<\/jats:p>","DOI":"10.1111\/dgd.12076","type":"journal-article","created":{"date-parts":[[2013,10,8]],"date-time":"2013-10-08T15:14:21Z","timestamp":1381245261000},"page":"699-709","source":"Crossref","is-referenced-by-count":11,"title":["<i>Cis<\/i>\u2010regulatory underpinnings of human <i>GLI3<\/i> expression in embryonic craniofacial structures and internal organs"],"prefix":"10.1111","volume":"55","author":[{"given":"Amir A.","family":"Abbasi","sequence":"first","affiliation":[{"name":"Faculty of Biological Sciences National Center for Bioinformatics Program of Comparative and Evolutionary Genomics Quaid\u2010i\u2010Azam University Islamabad 45320 Pakistan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rashid","family":"Minhas","sequence":"additional","affiliation":[{"name":"Faculty of Biological Sciences National Center for Bioinformatics Program of Comparative and Evolutionary Genomics Quaid\u2010i\u2010Azam University Islamabad 45320 Pakistan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ansgar","family":"Schmidt","sequence":"additional","affiliation":[{"name":"Department of Pathology Philipps\u2010Universit\u00e4t Marburg 35033 Marburg Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sabine","family":"Koch","sequence":"additional","affiliation":[{"name":"Department of Pathology Philipps\u2010Universit\u00e4t Marburg 35033 Marburg Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Karl\u2010Heinz","family":"Grzeschik","sequence":"additional","affiliation":[{"name":"Department of Human Genetics Philipps\u2010Universit\u00e4t Marburg 35037 Marburg Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2013,9,19]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ympev.2010.07.021"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1002\/dvdy.22572"},{"key":"e_1_2_9_4_1","doi-asserted-by":"crossref","first-page":"5","DOI":"10.4137\/EBO.S2322","article-title":"Evolution and functional diversification of the GLI family of transcription factors in vertebrates","volume":"5","author":"Abbasi A. 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