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

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.

scholarly journals Persistent Ventricle Partitioning in the Adult Zebrafish Heart

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.

scholarly journals Persistent ventricle partitioning in the adult zebrafish heart

2021 ◽  
Author(s):  
Catherine Pfefferli ◽  
Hannah R. Moran ◽  
Anastasia Felker ◽  
Christian Mosimann ◽  
Anna Jazwinska
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) 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 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.

scholarly journals The amphibian second heart field: Xenopus islet-1 is required for cardiovascular development

2007 ◽  
Vol 311 (2) ◽  
pp. 297-310 ◽  
Author(s):  
Thomas Brade ◽  
Susanne Gessert ◽  
Michael Kühl ◽  
Petra Pandur
Keyword(s):  
Cardiovascular Development ◽  
Second Heart Field ◽  
Heart Field ◽  
Islet 1

scholarly journals Hippo signaling determines the number of venous pole cells that originate from the anterior lateral plate mesoderm in zebrafish

eLife ◽  
2018 ◽  
Vol 7 ◽  
Author(s):  
Hajime Fukui ◽  
Takahiro Miyazaki ◽  
Renee Wei-Yan Chow ◽  
Hiroyuki Ishikawa ◽  
Hiroyuki Nakajima ◽  
...  
Keyword(s):  
Cell Number ◽  
Bmp Signaling ◽  
Hippo Signaling ◽  
Lateral Plate Mesoderm ◽  
Cardiomyocyte Proliferation ◽  
Heart Tube ◽  
Lateral Plate ◽  
Large Tumor ◽  
Developmental Potential ◽  
Anterior Lateral Plate Mesoderm

The differentiation of the lateral plate mesoderm cells into heart field cells constitutes a critical step in the development of cardiac tissue and the genesis of functional cardiomyocytes. Hippo signaling controls cardiomyocyte proliferation, but the role of Hippo signaling during early cardiogenesis remains unclear. Here, we show that Hippo signaling regulates atrial cell number by specifying the developmental potential of cells within the anterior lateral plate mesoderm (ALPM), which are incorporated into the venous pole of the heart tube and ultimately into the atrium of the heart. We demonstrate that Hippo signaling acts through large tumor suppressor kinase 1/2 to modulate BMP signaling and the expression of hand2, a key transcription factor that is involved in the differentiation of atrial cardiomyocytes. Collectively, these results demonstrate that Hippo signaling defines venous pole cardiomyocyte number by modulating both the number and the identity of the ALPM cells that will populate the atrium of the heart.

scholarly journals Zebrafish second heart field development relies on progenitor specification in anterior lateral plate mesoderm and nkx2.5 function

Development ◽  
2013 ◽  
Vol 140 (6) ◽  
pp. 1353-1363 ◽  
Author(s):  
B. Guner-Ataman ◽  
N. Paffett-Lugassy ◽  
M. S. Adams ◽  
K. R. Nevis ◽  
L. Jahangiri ◽  
...  
Keyword(s):  
Lateral Plate Mesoderm ◽  
Lateral Plate ◽  
Field Development ◽  
Second Heart Field ◽  
Heart Field ◽  
Anterior Lateral Plate Mesoderm

scholarly journals Cardiac progenitors auto-regulate second heart field cell fate via Wnt secretion

2021 ◽  
Author(s):  
Matthew Miyamoto ◽  
Suraj Kannan ◽  
Hideki Uosaki ◽  
Tejasvi Kakani ◽  
Sean Murphy ◽  
...  
Keyword(s):  
Single Cell ◽  
Cell Fate ◽  
Congenital Heart ◽  
Heart Defects ◽  
Cardiac Marker ◽  
Cardiac Progenitors ◽  
Second Heart Field ◽  
Heart Field ◽  
Heart Formation

Proper heart formation requires coordinated development of two anatomically distinct groups of cells - the first and second heart fields (FHF and SHF). Given that congenital heart defects are often restricted to derivatives of the FHF or SHF, it is crucial to understand the mechanisms controlling their development. Wnt signaling has previously been implicated in SHF proliferation; however, the source of Wnts remains unknown. Through comparative gene analysis, we found upregulation of Wnts and Wnt receptor/target genes in the FHF and SHF, respectively, raising the possibility that early cardiac progenitors may secrete Wnts to influence SHF cell fate. To probe this further, we deleted Wntless (Wls), a gene required for Wnt ligand secretion, in various populations of precardiac cells. Deletion of Wls in Mesp1+ cells resulted in formation of a single chamber heart with left ventricle identity, implying compromised SHF development. This phenotype was recapitulated by deleting Wls in cells expressing Islet1, a pan-cardiac marker. Similarly, Wls deletion in cells expressing Nkx2.5, a later-expressed pan-cardiac marker, resulted in hypoplastic right ventricle, a structure derived from the SHF. However, no developmental defects were observed when deleting Wls in SHF progenitors. To gain mechanistic insights, we isolated Mesp1-lineage cells from developing embryos and performed single-cell RNA-sequencing. Our comprehensive single cell transcriptome analysis revealed that Wls deletion dysregulates developmental trajectories of both anterior and posterior SHF cells, marked by impaired proliferation and premature differentiation. Together, these results demonstrate a critical role of local precardiac mesodermal Wnts in SHF fate decision, providing fundamental insights into understanding heart field development and chamber formation.Significance StatementThere is significant interest in understanding the mechanisms underlying heart formation to develop treatments and cures for patients suffering from congenital heart disease. In particular, we were interested in the intricacies of first (FHF) and second heart field (SHF) development, as many congenital heart defects present with heart field-specific etiologies. Here, we uncovered a novel relationship between specified cardiac progenitor cells and second heart field progenitors. Through genetic manipulation of Wnt secretion in developing mouse embryos, we identified a population of cardiac progenitor cells that acts as a local source of Wnts which are necessary for proper SHF development. Our single cell transcriptomic analysis of developing anterior mesoderm showed cardiac progenitor-secreted Wnts function through regulation of differentiation and proliferation among SHF progenitors. Thus, this study provides insight into the source and timing of Wnts required for SHF development, and points to the crucial role of co-developing cell populations in heart development.

Abstract 322: Postnatal Islet-1 Cardioblasts Are of Neural Crest and Not Second Heart-Field Lineage

2016 ◽  
Vol 119 (suppl_1) ◽  
Author(s):  
Konstantinos E Hatzistergos ◽  
Joshua M Hare
Keyword(s):  
Neural Crest ◽  
Reporter Gene ◽  
Embryoid Body ◽  
Temporal Analysis ◽  
Lineage Tracing ◽  
Gene Activity ◽  
Reporter Gene Activity ◽  
Second Heart Field ◽  
Heart Field ◽  
Islet 1

Introduction: The transcription factor Islet-1 (Isl1) is expressed in cardiac mesodermal and neural crest (CNC) lineages during cardiogenesis. A pool of Isl1 + cells persist in the perinatal heart (Isl1 + CPCs), some of which are touted as residual second heart-field (SHF)- derived cardioblasts. However, direct lineage-tracing evidence, supporting a SHF over a CNC origin of Isl1 + CPCs, are lacking. Hypothesis: Isl1 + CPCs are of CNC and not SHF lineage. Methods: The Isl1-nLacZ, Wnt1-Cre;tdTomato and Wnt1::FlpE;RC::Fela mice, and iPSCs derived from Wnt1-Cre;tdTomato mice (iPSC Wnt1 ) were employed to lineage-trace Isl1 + CPCs. Results: Temporal analysis of Isl1-nLacZ embryos illustrated a transient, stage-specific reporter gene activity in mesendodermal and neuroectodermal cells. Particularly, at embryonic day (E)9.5, reporter gene activity (x-gal), was strong in the outflow tract (OFT), and exhibited a weak, spotty pattern in the heart. At E12.5, x-gal was strong in the neural tube (NT); reduced in the OFT; and undetectable in the heart. Isl1 immunohistochemistry (IHC) illustrated similar activity of x-gal with endogenous Isl1 expression. Importantly, x-gal remained permanently undetected in the heart. Isl1 IHC in E12.5 Wnt1-Cre;tdTomato and Wnt1::FlpE;RC::Fela embryos indicated that Isl1 + cells in the OFT and NT colocalized with Wnt1 reporter transgenes. At E18.5 and postnatal day 1 (PN1), Isl1 + cells were exclusively of Wnt1 lineage, indicating that Isl1 + CPCs are CNC- and not SHF-derived. Since CNCs minimally contribute cardiomyocytes in mammals, a presumptive full cardiomyogenic capacity of Isl1 + CPCs potentially contrasts with a CNC origin. To address this controversy, we differentiated iPSC Wnt1 toward the CNC lineage, using a previously established embryoid body (EB) differentiation protocol involving transient BMP antagonism. At ~EB-day 9, tdTomato + /Isl1 + CNCs emerged, which progressively differentiated into spontaneously beating, Nkx2.5 + cardiomyocytes. Conclusions: Our findings clarify that Isl1 + CPCs are of CNC and not SHF origin, and suggest a novel role of the mammalian CNC, as a contributor of long-lived myocardial progenitors that could be targeted for heart-related therapeutic purposes.

scholarly journals Genetic and Cellular Interaction During Cardiovascular Development Implicated in Congenital Heart Diseases

2021 ◽  
Vol 8 ◽  
Author(s):  
Kazuki Kodo ◽  
Keiko Uchida ◽  
Hiroyuki Yamagishi
Keyword(s):  
Neural Crest ◽  
Congenital Heart ◽  
Cellular Interaction ◽  
Cardiovascular Development ◽  
Cardiac Neural Crest ◽  
Second Heart Field ◽  
Genomic Architecture ◽  
Heart Field ◽  
First Heart Field ◽  
Mutation Analyses

Congenital heart disease (CHD) is the most common life-threatening congenital anomaly. CHD occurs due to defects in cardiovascular development, and the majority of CHDs are caused by a multifactorial inheritance mechanism, which refers to the interaction between genetic and environmental factors. During embryogenesis, the cardiovascular system is derived from at least four distinct cell lineages: the first heart field, second heart field, cardiac neural crest, and proepicardial organ. Understanding the genes involved in each lineage is essential to uncover the genomic architecture of CHD. Therefore, we provide an overview of recent research progress using animal models and mutation analyses to better understand the molecular mechanisms and pathways linking cardiovascular development and CHD. For example, we highlight our recent work on genes encoding three isoforms of inositol 1,4,5-trisphosphate receptors (IP3R1, 2, and 3) that regulate various vital and developmental processes, which have genetic redundancy during cardiovascular development. Specifically, IP3R1 and 2 have redundant roles in the atrioventricular cushion derived from the first heart field lineage, whereas IP3R1 and 3 exhibit redundancy in the right ventricle and the outflow tract derived from the second heart field lineage, respectively. Moreover, 22q11.2 deletion syndrome (22q11DS) is highly associated with CHD involving the outflow tract, characterized by defects of the cardiac neural crest lineage. However, our studies have shown that TBX1, a major genetic determinant of 22q11DS, was not expressed in the cardiac neural crest but rather in the second heart field, suggesting the importance of the cellular interaction between the cardiac neural crest and the second heart field. Comprehensive genetic analysis using the Japanese genome bank of CHD and mouse models revealed that a molecular regulatory network involving GATA6, FOXC1/2, TBX1, SEMA3C, and FGF8 was essential for reciprocal signaling between the cardiac neural crest and the second heart field during cardiovascular development. Elucidation of the genomic architecture of CHD using induced pluripotent stem cells and next-generation sequencing technology, in addition to genetically modified animal models and human mutation analyses, would facilitate the development of regenerative medicine and/or preventive medicine for CHD in the near future.

scholarly journals HCN4 Dynamically Marks the First Heart Field and Conduction System Precursors

2013 ◽  
Vol 113 (4) ◽  
pp. 399-407 ◽  
Author(s):  
Xingqun Liang ◽  
Gang Wang ◽  
Lizhu Lin ◽  
Jennifer Lowe ◽  
Qingquan Zhang ◽  
...  
Keyword(s):  
Conduction System ◽  
Heart Field ◽  
First Heart Field
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