title: Distinct enhancer elements control Hex expression during gastrulation and early organogenesis.
abstract: In the mouse, embryological and genetic studies have indicated that two spatially distinct signalling centres, the anterior visceral endoderm and the node and its derivatives, are required for the correct patterning of the anterior neural ectoderm. The divergent homeobox gene Hex is expressed in the anterior visceral endoderm, in the node (transiently), and in the anterior definitive endoderm. Other sites of Hex expression include the liver and thyroid primordia and the endothelial cell precursors. We have used transgenic analysis to map the cis-acting regulatory elements controlling Hex expression during early mouse development. A 4.2-kb upstream region is important for Hex expression in the endothelial cell precursors, liver, and thyroid, and a 633-bp intronic fragment is both necessary and sufficient for Hex expression in the anterior visceral endoderm and the anterior definitive endoderm. These same regions drive expression in homologous structures in Xenopus laevis, indicating conservation of these regulatory regions in vertebrates. Analysis of the anterior visceral endoderm/anterior definitive endoderm enhancer identifies a repressor region that is required to downregulate Hex expression in the node once the anterior definitive endoderm has formed. This analysis also reveals that the initiation of Hex expression in the anterior visceral endoderm and axial mesendoderm requires common elements, but maintenance of expression is regulated independently in these tissues.
authors.affiliation: Division of Mammalian Development, National Institute for Medical Research, The Ridgeway, Mill Hill, London, NW7 1AA, United Kingdom.
authors.forename: T A
authors.initials: TA
authors.lastname: Rodriguez
authors.forename: E S
authors.initials: ES
authors.lastname: Casey
authors.forename: R M
authors.initials: RM
authors.lastname: Harland
authors.forename: J C
authors.initials: JC
authors.lastname: Smith
authors.forename: R S
authors.initials: RS
authors.lastname: Beddington
mesh_terms: D000818:Animals; D030801:Animals, Genetically Modified; D001483:Base Sequence; D019521:Body Patterning; D004627:Embryonic Induction; D005314:Embryonic and Fetal Development / Q000235:genetics*; D004707:Endoderm; D004730:Endothelium, Vascular / Q000196:embryology; D004742:Enhancer Elements, Genetic; D005775:Gastrula; D005786:Gene Expression Regulation; D018398:Homeodomain Proteins / Q000235:genetics*; D008099:Liver / Q000196:embryology; D008648:Mesoderm; D051379:Mice; D008969:Molecular Sequence Data; D013045:Species Specificity; D013961:Thyroid Gland / Q000196:embryology; D014018:Tissue Distribution; D014157:Transcription Factors; D029867:Xenopus Proteins
chemical_list: C513080:Hhex protein, mouse; D018398:Homeodomain Proteins; D014157:Transcription Factors; D029867:Xenopus Proteins; C513078:hhex protein, Xenopus