title: A Tlx2-Cre mouse line uncovers essential roles for hand1 in extraembryonic and lateral mesoderm.
abstract: Hand1 regulates development of numerous tissues within the embryo, extraembryonic mesoderm, and trophectoderm. Systemic loss of Hand1 results in early embryonic lethality but the cause has remained unknown. To determine if Hand1 expression in extraembryonic mesoderm is essential for embryonic survival, Hand1 was conditionally deleted using the HoxB6-Cre mouse line that expresses Cre in extraembryonic and lateral mesoderm. Deletion of Hand1 using HoxB6-Cre resulted in embryonic lethality identical to systemic knockout. To determine if lethality is due to Hand1 function in extraembryonic mesoderm or lateral mesoderm, we generated a Tlx2-Cre mouse line expressing Cre in lateral mesoderm but not extraembryonic tissues. Deletion of Hand1 using the Tlx2-Cre line results in embryonic survival with embryos exhibiting herniated gut and thin enteric smooth muscle. Our results show that Hand1 regulates development of lateral mesoderm derivatives and its loss in extraembryonic mesoderm is the primary cause of lethality in Hand1-null embryos.
authors.forename: Emily L
authors.initials: EL
authors.lastname: Maska
authors.forename: Peter
authors.initials: P
authors.lastname: Cserjesi
authors.forename: Lisa L
authors.initials: LL
authors.lastname: Hua
authors.forename: Meghan E
authors.initials: ME
authors.lastname: Garstka
authors.forename: Heather M
authors.initials: HM
authors.lastname: Brody
authors.forename: Yuka
authors.initials: Y
authors.lastname: Morikawa
mesh_terms: D000818:Animals; D051792:Basic Helix-Loop-Helix Proteins / Q000235:genetics / Q000502:physiology*; D004622:Embryo, Mammalian / Q000196:embryology* / Q000378:metabolism; D005260:Female; D041981:Gastrointestinal Tract / Q000002:abnormalities / Q000378:metabolism; D018507:Gene Expression Regulation, Developmental; D018398:Homeodomain Proteins / Q000235:genetics / Q000378:metabolism*; D007150:Immunohistochemistry; D019426:Integrases / Q000235:genetics / Q000378:metabolism; D007763:Lac Operon / Q000235:genetics; D008297:Male; D008648:Mesoderm / Q000196:embryology* / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008822:Mice, Transgenic; D001616:beta-Galactosidase / Q000378:metabolism
chemical_list: D051792:Basic Helix-Loop-Helix Proteins; D018398:Homeodomain Proteins; D019426:Integrases; D001616:beta-Galactosidase; C095572:Hand1 protein, mouse; C490537:Hoxb6 protein, mouse; C107836:Tlx2 protein, mouse; C045073:Cre recombinase