DM-GRASP/ALCAM/CD166 is required for cardiac morphogenesis and maintenance of cardiac identity in first heart field derived cells

AbstractDuring early vertebrate heart development, the heart transitions from a linear tube to a complex asymmetric structure. This process includes looping of the tube and ballooning of the emerging cardiac chambers, which occur simultaneously with growth of the heart. A key driver of cardiac growth is deployment of cells from the Second Heart Field (SHF) into both poles of the heart, with cardiac morphogenesis and growth intimately linked in heart development. Laminin is a core component of extracellular matrix (ECM) basement membranes, and although mutations in specific laminin subunits are linked with a variety of cardiac abnormalities, including congenital heart disease and dilated cardiomyopathy, no role for laminin has been identified in early vertebrate heart morphogenesis. We identified dynamic, tissue-specific expression of laminin subunit genes in the developing zebrafish heart, supporting a role for laminins in heart morphogenesis.lamb1amutants exhibit cardiomegaly from 2dpf onwards, with subsequent progressive defects in cardiac morphogenesis characterised by a failure of the chambers to compact around the developing atrioventricular canal. We show that loss oflamb1aresults in excess addition of SHF cells to the atrium, revealing that Lamb1a functions to limit heart size during cardiac development by restricting SHF addition to the venous pole.lamb1amutants exhibit hallmarks of altered haemodynamics, and specifically blocking cardiac contractility inlamb1amutants rescues heart size and atrial SHF addition. Furthermore, we identify that FGF and RA signalling, two conserved pathways promoting SHF addition, are regulated by heart contractility and are dysregulated inlamb1amutants, suggesting that laminin mediates interactions between SHF deployment, heart biomechanics, and biochemical signalling during heart development. Together, this describes the first requirement for laminins in early vertebrate heart morphogenesis, reinforcing the importance of specialised ECM composition in cardiac development.

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Tbx1 affects asymmetric cardiac morphogenesis by regulating Pitx2 in the secondary heart field

Development ◽

10.1242/dev.02309 ◽

2006 ◽

Vol 133 (8) ◽

pp. 1565-1573 ◽

Cited By ~ 106

Author(s):

S. Nowotschin

Keyword(s):

Cardiac Morphogenesis ◽

Heart Field ◽

Secondary Heart Field

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Hippo signaling restricts cells in the second heart field that differentiate into Islet-1-positive atrial cardiomyocytes

10.1101/154765 ◽

2017 ◽

Author(s):

Hajime Fukui ◽

Takahiro Miyazaki ◽

Hiroyuki Ishikawa ◽

Hiroyuki Nakajima ◽

Naoki Mochizuki

Keyword(s):

Hippo Signaling ◽

Lateral Plate ◽

Large Tumor ◽

Atrial Cardiomyocytes ◽

Second Heart Field ◽

Kinase Cascade ◽

Heart Field ◽

Heart Formation ◽

First Heart Field ◽

Islet 1

AbstractCardiac precursor cells (CPCs) in the first heart field (FHF) and the second heart field (SHF) present at both arterial and venous poles assemble to form a cardiac tube in zebrafish. Hippo kinase cascade is essential for proper heart formation; however, it remains elusive how Hippo signal contributes to early cardiac fate determination. We here demonstrate that mutants of large tumor suppressor kinase 1/2 (lats1/2) exhibited an increase in a SHF marker, Islet1 (Isl1)-positive and hand2 promoter-activated venous pole atrial cardiomyocytes (CMs) and that those showed expansion of the domain between between the anterior and the posterior lateral plate mesoderm. Consistently, TEAD-8 dependent transcription was activated in caudal region of the left ALPM cells that gave rise to the venous pole atrial CMs. Yap1/Wwtr1-promoted bmp2b expression was essential for Smad-regulated hand2 expression in the left ALPM, indicating that Hippo signaling restricts the SHF cells originating from the left ALPM that move toward the venous pole.

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Faculty Opinions recommendation of HCN4 dynamically marks the first heart field and conduction system precursors.

Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature ◽

10.3410/f.718030772.793480274 ◽

2013 ◽

Author(s):

Glenn Fishman ◽

Karen Maass

Keyword(s):

Conduction System ◽

Heart Field ◽

First Heart Field

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Numb family proteins: novel players in cardiac morphogenesis and cardiac progenitor cell differentiation

BioMolecular Concepts ◽

10.1515/bmc-2015-0003 ◽

2015 ◽

Vol 6 (2) ◽

pp. 137-148 ◽

Cited By ~ 11

Author(s):

Mingfu Wu ◽

Jingjing Li

Keyword(s):

Cell Differentiation ◽

Progenitor Cell ◽

Cardiac Development ◽

Heart Diseases ◽

Adaptor Protein ◽

Asymmetric Distribution ◽

Heart Tube ◽

Cardiac Morphogenesis ◽

Cardiac Progenitor Cell ◽

Heart Field

AbstractVertebrate heart formation is a spatiotemporally regulated morphogenic process that initiates with bilaterally symmetric cardiac primordial cells migrating toward the midline to form a linear heart tube. The heart tube then elongates and undergoes a series of looping morphogenesis, followed by expansions of regions that are destined to become primitive heart chambers. During the cardiac morphogenesis, cells derived from the first heart field contribute to the primary heart tube, and cells from the secondary heart field, cardiac neural crest, and pro-epicardial organ are added to the heart tube in a precise spatiotemporal manner. The coordinated addition of these cells and the accompanying endocardial cushion morphogenesis yield the atrial, ventricular, and valvular septa, resulting in the formation of a four-chambered heart. Perturbation of progenitor cells’ deployment and differentiation leads to a spectrum of congenital heart diseases. Two of the genes that were recently discovered to be involved in cardiac morphogenesis are Numb and Numblike. Numb, an intracellular adaptor protein, distinguishes sibling cell fates by its asymmetric distribution between the two daughter cells and its ability to inhibit Notch signaling. Numb regulates cardiac progenitor cell differentiation in Drosophila and controls heart tube laterality in Zebrafish. In mice, Numb and Numblike, the Numb family proteins (NFPs), function redundantly and have been shown to be essential for epicardial development, cardiac progenitor cell differentiation, outflow tract alignment, atrioventricular septum morphogenesis, myocardial trabeculation, and compaction. In this review, we will summarize the functions of NFPs in cardiac development and discuss potential mechanisms of NFPs in the regulation of cardiac development.

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HCN4 Charges Up the First Heart Field

Circulation Research ◽

10.1161/circresaha.113.301981 ◽

2013 ◽

Vol 113 (4) ◽

pp. 350-351 ◽

Cited By ~ 3

Author(s):

Sean M. Stevens ◽

William T. Pu

Keyword(s):

Heart Field ◽

First Heart Field

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Persistent Ventricle Partitioning in the Adult Zebrafish Heart

Journal of Cardiovascular Development and Disease ◽

10.3390/jcdd8040041 ◽

2021 ◽

Vol 8 (4) ◽

pp. 41

Author(s):

Catherine Pfefferli ◽

Hannah R. Moran ◽

Anastasia Felker ◽

Christian Mosimann ◽

Anna Jaźwińska

Keyword(s):

Lateral Plate Mesoderm ◽

Adult Zebrafish ◽

Lateral Plate ◽

Second Heart Field ◽

Heart Field ◽

Left And Right ◽

First Heart Field ◽

The Right ◽

Physical Boundary ◽

Zebrafish Heart

The vertebrate heart integrates cells from the early-differentiating first heart field (FHF) and the later-differentiating second heart field (SHF), both emerging from the lateral plate mesoderm. In mammals, this process forms the basis for the development of the left and right ventricle chambers and subsequent chamber septation. The single ventricle-forming zebrafish heart also integrates FHF and SHF lineages during embryogenesis, yet the contributions of these two myocardial lineages to the adult zebrafish heart remain incompletely understood. Here, we characterize the myocardial labeling of FHF descendants in both the developing and adult zebrafish ventricle. Expanding previous findings, late gastrulation-stage labeling using drl-driven CreERT2 recombinase with a myocardium-specific, myl7-controlled, loxP reporter results in the predominant labeling of FHF-derived outer curvature and the right side of the embryonic ventricle. Raised to adulthood, such lineage-labeled hearts retain broad areas of FHF cardiomyocytes in a region of the ventricle that is positioned at the opposite side to the atrium and encompasses the apex. Our data add to the increasing evidence for a persisting cell-based compartmentalization of the adult zebrafish ventricle even in the absence of any physical boundary.

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