Journal Article

Chamber identity programs drive early functional partitioning of the heart

Mosimann, Christian, Burns, C. Geoffrey, Carr, Logan A., Zon, Leonard I., Nevis, Kathleen R., Burns, Caroline E., DiBiase, Anthony, Burger, Alexa, MacRae, Calum A., Werdich, Andreas A., Lawson, Katy L., Musso, Gabriel, Zhou, Yi, Panáková, Daniela, Sabeh, M. Khaled, Davidson, Alan J.

2015

Overview

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. The heart forms from combining the first with the second heart field, which in mammals creates left and right ventricle. Here transgenic zebrafish and physiology studies reveal that transcription factors controlling septation in mammals already in teleosts guide muscle coupling by controlling the relative contribution of the two fields to the heart.

• Publisher: Nature Publishing Group UK,Nature Publishing Group,Nature Pub. Group
• Subject: 14/19 / 14/35 / 14/63 / 38/43 / 38/44 / 38/61 / 38/77 / 631/136 / 631/136/334/1874/763 / 631/443/592 / 64/116 / 96/34 / Animals / Animals, Genetically Modified / Cadherins - genetics / Cadherins - metabolism / Electrical properties / Embryo, Nonmammalian / Gene Expression Regulation, Developmental / Heart - embryology / Heart Atria - embryology / Heart Atria - metabolism / Heart Ventricles - embryology / Heart Ventricles - metabolism / Humanities and Social Sciences / Latent TGF-beta Binding Proteins - genetics / Latent TGF-beta Binding Proteins - metabolism / LIM Domain Proteins - genetics / LIM Domain Proteins - metabolism / Mesoderm - embryology / Mesoderm - metabolism / multidisciplinary / Myocardium - metabolism / Myocytes, Cardiac - metabolism / Myosin Light Chains - genetics / Myosin Light Chains - metabolism / Regulatory Elements, Transcriptional - genetics / Salivary Proteins and Peptides - genetics / Salivary Proteins and Peptides - metabolism / Science / Science (multidisciplinary) / T-Box Domain Proteins - genetics / T-Box Domain Proteins - metabolism / Transcription Factors - genetics / Transcription Factors - metabolism / Zebrafish / Zebrafish Proteins - genetics / Zebrafish Proteins - metabolism