title: Early patterning and specification of cardiac progenitors in gastrulating mesoderm.
abstract: Mammalian heart development requires precise allocation of cardiac progenitors. The existence of a multipotent progenitor for all anatomic and cellular components of the heart has been predicted but its identity and contribution to the two cardiac progenitor 'fields' has remained undefined. Here we show, using clonal genetic fate mapping, that Mesp1+ cells in gastrulating mesoderm are rapidly specified into committed cardiac precursors fated for distinct anatomic regions of the heart. We identify Smarcd3 as a marker of early specified cardiac precursors and identify within these precursors a compartment boundary at the future junction of the left and right ventricles that arises prior to morphogenesis. Our studies define the timing and hierarchy of cardiac progenitor specification and demonstrate that the cellular and anatomical fate of mesoderm-derived cardiac cells is specified very early. These findings will be important to understand the basis of congenital heart defects and to derive cardiac regeneration strategies.
authors.affiliation: Gladstone Institute of Cardiovascular Disease, San Francisco, United States.
authors.forename: W Patrick
authors.initials: WP
authors.lastname: Devine
authors.affiliation: Gladstone Institute of Cardiovascular Disease, San Francisco, United States.
authors.forename: Joshua D
authors.initials: JD
authors.lastname: Wythe
authors.affiliation: Gladstone Institute of Cardiovascular Disease, San Francisco, United States.
authors.forename: Matthew
authors.initials: M
authors.lastname: George
authors.affiliation: Gladstone Institute of Cardiovascular Disease, San Francisco, United States.
authors.forename: Kazuko
authors.initials: K
authors.lastname: Koshiba-Takeuchi
authors.affiliation: Gladstone Institute of Cardiovascular Disease, San Francisco, United States.
authors.forename: Benoit G
authors.initials: BG
authors.lastname: Bruneau
mesh_terms: D000818:Animals; D051792:Basic Helix-Loop-Helix Proteins / Q000378:metabolism; D019521:Body Patterning; D002868:Chromosomal Proteins, Non-Histone / Q000378:metabolism; D002999:Clone Cells; D004622:Embryo, Mammalian / Q000378:metabolism; D053595:Embryonic Stem Cells / Q000166:cytology* / Q000378:metabolism; D004742:Enhancer Elements, Genetic / Q000235:genetics; D054262:Gastrulation; D006321:Heart / Q000196:embryology*; D006352:Heart Ventricles / Q000196:embryology / Q000378:metabolism; D019426:Integrases / Q000378:metabolism; D008648:Mesoderm / Q000166:cytology / Q000196:embryology*; D051379:Mice; D008954:Models, Biological; D009124:Muscle Proteins / Q000378:metabolism; D009206:Myocardium / Q000166:cytology; D009928:Organ Specificity / Q000235:genetics
chemical_list: D051792:Basic Helix-Loop-Helix Proteins; D002868:Chromosomal Proteins, Non-Histone; D019426:Integrases; D009124:Muscle Proteins; C101538:Mesp1 protein, mouse; C494055:Smarcd3 protein, mouse; C045073:Cre recombinase
keywords: developmental biology; embryo; heart; lineages; mesoderm; mouse; stem cells