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Nat Commun. 2015 Aug 26;6:8146. doi: 10.1038/ncomms9146.

Chamber identity programs drive early functional partitioning of the heart.

Author information

1
Howard Hughes Medical Institute, Boston, Massachusetts 02115, USA.
2
Stem Cell Program, Boston Children's Hospital, Boston, Massachusetts 02115, USA.
3
Division of Hematology/Oncology, Boston Children's Hospital, Harvard Stem Cell Institute, Harvard Medical School, Boston, Massachusetts 02115, USA.
4
Institute of Molecular Life Sciences (IMLS), University of Zürich, 8057 Zürich, Switzerland.
5
Cardiovascular Division, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts 02115, USA.
6
Cardiovascular Research Center, Massachusetts General Hospital, Harvard Medical School, Charlestown, Massachusetts 02129, USA.

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.

PMID:
26306682
PMCID:
PMC4560818
DOI:
10.1038/ncomms9146
[Indexed for MEDLINE]
Free PMC Article

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