title: Mesodermal Nkx2.5 is necessary and sufficient for early second heart field development.
abstract: The vertebrate heart develops from mesoderm and requires inductive signals secreted from early endoderm. During embryogenesis, Nkx2.5 acts as a key transcription factor and plays essential roles for heart formation from Drosophila to human. In mice, Nkx2.5 is expressed in the early first heart field, second heart field pharyngeal mesoderm, as well as pharyngeal endodermal cells underlying the second heart field. Currently, the specific requirements for Nkx2.5 in the endoderm versus mesoderm with regard to early heart formation are incompletely understood. Here, we performed tissue-specific deletion in mice to dissect the roles of Nkx2.5 in the pharyngeal endoderm and mesoderm. We found that heart development appeared normal after endodermal deletion of Nkx2.5 whereas mesodermal deletion engendered cardiac defects almost identical to those observed on Nkx2.5 null embryos (Nkx2.5(-/-)). Furthermore, re-expression of Nkx2.5 in the mesoderm rescued Nkx2.5(-/-) heart defects. Our findings reveal that Nkx2.5 in the mesoderm is essential while endodermal expression is dispensable for early heart formation in mammals.
authors.affiliation: Department of Developmental and Regenerative Biology, The Mindich Child Health and Development Institute, and The Black Family Stem Cell Institute, Icahn School of Medicine at Mount Sinai, One Gustave L. Levy Place, New York, NY 10029, USA.
authors.forename: Lu
authors.initials: L
authors.lastname: Zhang
authors.affiliation: Department of Developmental and Regenerative Biology, The Mindich Child Health and Development Institute, and The Black Family Stem Cell Institute, Icahn School of Medicine at Mount Sinai, One Gustave L. Levy Place, New York, NY 10029, USA.
authors.forename: Aya
authors.initials: A
authors.lastname: Nomura-Kitabayashi
authors.affiliation: Department of Developmental and Regenerative Biology, The Mindich Child Health and Development Institute, and The Black Family Stem Cell Institute, Icahn School of Medicine at Mount Sinai, One Gustave L. Levy Place, New York, NY 10029, USA.
authors.forename: Nishat
authors.initials: N
authors.lastname: Sultana
authors.affiliation: Department of Developmental and Regenerative Biology, The Mindich Child Health and Development Institute, and The Black Family Stem Cell Institute, Icahn School of Medicine at Mount Sinai, One Gustave L. Levy Place, New York, NY 10029, USA.
authors.forename: Weibin
authors.initials: W
authors.lastname: Cai
authors.affiliation: Department of Developmental and Regenerative Biology, The Mindich Child Health and Development Institute, and The Black Family Stem Cell Institute, Icahn School of Medicine at Mount Sinai, One Gustave L. Levy Place, New York, NY 10029, USA.
authors.forename: Xiaoqiang
authors.initials: X
authors.lastname: Cai
authors.affiliation: Weis Center for Research, 100 North Academy Avenue, Danville, PA 17822, USA.
authors.forename: Anne M
authors.initials: AM
authors.lastname: Moon
authors.affiliation: Department of Developmental and Regenerative Biology, The Mindich Child Health and Development Institute, and The Black Family Stem Cell Institute, Icahn School of Medicine at Mount Sinai, One Gustave L. Levy Place, New York, NY 10029, USA. Electronic address: chenleng.cai@mssm.edu.
authors.forename: Chen-Leng
authors.initials: CL
authors.lastname: Cai
mesh_terms: D000818:Animals; D004622:Embryo, Mammalian / Q000196:embryology / Q000378:metabolism / Q000648:ultrastructure; D004707:Endoderm / Q000196:embryology / Q000378:metabolism; D005260:Female; D018507:Gene Expression Regulation, Developmental; D006321:Heart / Q000196:embryology*; D000072576:Homeobox Protein Nkx-2.5; D018398:Homeodomain Proteins / Q000235:genetics* / Q000378:metabolism; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D008648:Mesoderm / Q000196:embryology / Q000378:metabolism*; D051379:Mice; D018345:Mice, Knockout; D008855:Microscopy, Electron, Scanning; D009206:Myocardium / Q000378:metabolism*; D010614:Pharynx / Q000196:embryology / Q000378:metabolism; D011247:Pregnancy; D013997:Time Factors; D014157:Transcription Factors / Q000235:genetics* / Q000378:metabolism
chemical_list: D000072576:Homeobox Protein Nkx-2.5; D018398:Homeodomain Proteins; C484469:Nkx2-5 protein, mouse; D014157:Transcription Factors
keywords: Heart development; Nkx2.5; Pharyngeal endoderm; Pharyngeal mesoderm; Second heart field