title: A novel regulatory element for Shh expression in the lung and gut of mouse embryos.
abstract: Hedgehog (Hh) signaling plays pivotal roles in morphogenesis of several embryonic tissues, including the primitive gut. In the mouse embryo, Sonic hedgehog (Shh) is expressed in endodermal epithelia from the oral cavity to the intestine, and contributes to cell proliferation in the underlying mesenchyme and subsequent differentiation into the gastrointestinal smooth muscle. Three evolutionary conserved non-coding sequences in the region upstream of the Shh coding sequence contain endoderm-specific enhancers for Shh expression. Although Shh expression in the endodermal epithelial lining is mostly attributed to these three enhancers, none of them regulates gene expression in the gastroesophageal epithelium. Here, we found that a 1.7Kb fragment located 100Kb upstream of the Shh coding sequence contains a functional element for Shh expression in endodermal organs, including the esophagus and stomach. Compared with the three known endodermal enhancers, this novel enhancer shows less evolutionary conservation, even among rodents. In mouse embryonic endodermal tissues, the seamless expression of Shh is achieved by a patchwork of multiple enhancers with different rates of evolution.
authors.affiliation: Department of Clinical and Laboratory Medicine, Faculty of Medicine, University of Yamanashi, 1111 Yata, Mishima, Shizuoka 411-8540, Japan.
authors.forename: Nagaharu
authors.initials: N
authors.lastname: Tsukiji
authors.affiliation: Mammalian Genetics Laboratory, Genetic Strains Research Center, National Institute of Genetics, 1111 Yata, Mishima, Shizuoka 411-8540, Japan.
authors.forename: Takanori
authors.initials: T
authors.lastname: Amano
authors.affiliation: Mammalian Genetics Laboratory, Genetic Strains Research Center, National Institute of Genetics, 1111 Yata, Mishima, Shizuoka 411-8540, Japan. Electronic address: tshiroishi@lab.nig.ac.jp.
authors.forename: Toshihiko
authors.initials: T
authors.lastname: Shiroishi
mesh_terms: D000818:Animals; D002454:Cell Differentiation / Q000235:genetics*; D004622:Embryo, Mammalian / Q000378:metabolism; D004707:Endoderm / Q000254:growth & development / Q000378:metabolism; D041981:Gastrointestinal Tract / Q000254:growth & development* / Q000378:metabolism; D018507:Gene Expression Regulation, Developmental; D053823:Hedgehog Proteins / Q000096:biosynthesis* / Q000235:genetics; D008168:Lung / Q000254:growth & development* / Q000378:metabolism; D008648:Mesoderm / Q000254:growth & development / Q000378:metabolism; D051379:Mice; D009024:Morphogenesis; D050436:Regulatory Elements, Transcriptional / Q000235:genetics*; D015398:Signal Transduction
chemical_list: D053823:Hedgehog Proteins; C465570:Shh protein, mouse
keywords: Conservation; Enhancer; Evolutionarily; Gene regulation; Mouse; Sonic hedgehog