title: Chamber identity programs drive early functional partitioning of the heart.
abstract: The vertebrate heart muscle (myocardium) develops from the first heart field (FHF) and expands by adding second heart field (SHF) cells. While both lineages exist already in teleosts, the primordial contributions of FHF and SHF to heart structure and function remain incompletely understood. Here we delineate the functional contribution of the FHF and SHF to the zebrafish heart using the cis-regulatory elements of the draculin (drl) gene. The drl reporters initially delineate the lateral plate mesoderm, including heart progenitors. Subsequent myocardial drl reporter expression restricts to FHF descendants. We harnessed this unique feature to uncover that loss of tbx5a and pitx2 affect relative FHF versus SHF contributions to the heart. High-resolution physiology reveals distinctive electrical properties of each heart field territory that define a functional boundary within the single zebrafish ventricle. Our data establish that the transcriptional program driving cardiac septation regulates physiologic ventricle partitioning, which successively provides mechanical advantages of sequential contraction.
authors: Howard Hughes Medical Institute, Boston, Massachusetts 02115, USA.|Stem Cell Program, Boston Children's Hospital, Boston, Massachusetts 02115, USA.|Division of Hematology/Oncology, Boston Children's Hospital, Harvard Stem Cell Institute, Harvard Medical School, Boston, Massachusetts 02115, USA.|Institute of Molecular Life Sciences (IMLS), University of Zürich, 8057 Zürich, Switzerland.
authors: Christian
authors: C
authors: Mosimann
authors: Cardiovascular Division, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts 02115, USA.
authors: Daniela
authors: D
authors: Panáková
authors: Cardiovascular Division, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts 02115, USA.
authors: Andreas A
authors: AA
authors: Werdich
authors: Cardiovascular Division, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts 02115, USA.
authors: Gabriel
authors: G
authors: Musso
authors: Institute of Molecular Life Sciences (IMLS), University of Zürich, 8057 Zürich, Switzerland.
authors: Alexa
authors: A
authors: Burger
authors: Howard Hughes Medical Institute, Boston, Massachusetts 02115, USA.|Stem Cell Program, Boston Children's Hospital, Boston, Massachusetts 02115, USA.|Division of Hematology/Oncology, Boston Children's Hospital, Harvard Stem Cell Institute, Harvard Medical School, Boston, Massachusetts 02115, USA.
authors: Katy L
authors: KL
authors: Lawson
authors: Howard Hughes Medical Institute, Boston, Massachusetts 02115, USA.|Stem Cell Program, Boston Children's Hospital, Boston, Massachusetts 02115, USA.|Division of Hematology/Oncology, Boston Children's Hospital, Harvard Stem Cell Institute, Harvard Medical School, Boston, Massachusetts 02115, USA.
authors: Logan A
authors: LA
authors: Carr
authors: Cardiovascular Research Center, Massachusetts General Hospital, Harvard Medical School, Charlestown, Massachusetts 02129, USA.
authors: Kathleen R
authors: KR
authors: Nevis
authors: Cardiovascular Division, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts 02115, USA.
authors: M Khaled
authors: MK
authors: Sabeh
authors: Howard Hughes Medical Institute, Boston, Massachusetts 02115, USA.|Stem Cell Program, Boston Children's Hospital, Boston, Massachusetts 02115, USA.|Division of Hematology/Oncology, Boston Children's Hospital, Harvard Stem Cell Institute, Harvard Medical School, Boston, Massachusetts 02115, USA.
authors: Yi
authors: Y
authors: Zhou
authors: Howard Hughes Medical Institute, Boston, Massachusetts 02115, USA.|Stem Cell Program, Boston Children's Hospital, Boston, Massachusetts 02115, USA.|Division of Hematology/Oncology, Boston Children's Hospital, Harvard Stem Cell Institute, Harvard Medical School, Boston, Massachusetts 02115, USA.
authors: Alan J
authors: AJ
authors: Davidson
authors: Howard Hughes Medical Institute, Boston, Massachusetts 02115, USA.|Stem Cell Program, Boston Children's Hospital, Boston, Massachusetts 02115, USA.|Division of Hematology/Oncology, Boston Children's Hospital, Harvard Stem Cell Institute, Harvard Medical School, Boston, Massachusetts 02115, USA.
authors: Anthony
authors: A
authors: DiBiase
authors: Cardiovascular Research Center, Massachusetts General Hospital, Harvard Medical School, Charlestown, Massachusetts 02129, USA.
authors: Caroline E
authors: CE
authors: Burns
authors: Cardiovascular Research Center, Massachusetts General Hospital, Harvard Medical School, Charlestown, Massachusetts 02129, USA.
authors: C Geoffrey
authors: CG
authors: Burns
authors: Cardiovascular Division, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts 02115, USA.
authors: Calum A
authors: CA
authors: MacRae
authors: Howard Hughes Medical Institute, Boston, Massachusetts 02115, USA.|Stem Cell Program, Boston Children's Hospital, Boston, Massachusetts 02115, USA.|Division of Hematology/Oncology, Boston Children's Hospital, Harvard Stem Cell Institute, Harvard Medical School, Boston, Massachusetts 02115, USA.
authors: Leonard I
authors: LI
authors: Zon
mesh_terms: D000818:Animals; D030801:Animals, Genetically Modified; D015820:Cadherins / Q000235:genetics / Q000378:metabolism; D004625:Embryo, Nonmammalian; D018507:Gene Expression Regulation, Developmental; D006321:Heart / Q000196:embryology; D006325:Heart Atria / Q000196:embryology* / Q000378:metabolism; D006352:Heart Ventricles / Q000196:embryology* / Q000378:metabolism; D060588:LIM Domain Proteins / Q000235:genetics / Q000378:metabolism; D053779:Latent TGF-beta Binding Proteins / Q000235:genetics / Q000378:metabolism; D008648:Mesoderm / Q000196:embryology / Q000378:metabolism; D009206:Myocardium / Q000378:metabolism*; D032383:Myocytes, Cardiac / Q000378:metabolism*; D018994:Myosin Light Chains / Q000235:genetics / Q000378:metabolism; D050436:Regulatory Elements, Transcriptional / Q000235:genetics; D012471:Salivary Proteins and Peptides / Q000235:genetics / Q000378:metabolism; D020825:T-Box Domain Proteins / Q000235:genetics / Q000378:metabolism; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism; D015027:Zebrafish; D029961:Zebrafish Proteins / Q000235:genetics* / Q000378:metabolism
chemical_list: C470286:CDH17 protein, zebrafish; D015820:Cadherins; D060588:LIM Domain Proteins; D053779:Latent TGF-beta Binding Proteins; C580770:Ltbp3 protein, zebrafish; D018994:Myosin Light Chains; C572614:Pitx2 protein, zebrafish; D012471:Salivary Proteins and Peptides; D020825:T-Box Domain Proteins; C103172:T-box transcription factor 5; D014157:Transcription Factors; D029961:Zebrafish Proteins; C094183:draculin; C513186:lmo2 protein, zebrafish