scholarly journals BMP-mediated inhibition of FGF signaling promotes cardiomyocyte differentiation of anterior heart field progenitors

Development ◽  
2010 ◽  
Vol 137 (18) ◽  
pp. 2989-3000 ◽  
Author(s):  
L. Tirosh-Finkel ◽  
A. Zeisel ◽  
M. Brodt-Ivenshitz ◽  
A. Shamai ◽  
Z. Yao ◽  
...  
Keyword(s):  
Cardiomyocyte Differentiation ◽  
Fgf Signaling ◽  
Heart Field ◽  
Anterior Heart Field

BMP-mediated inhibition of FGF signaling promotes cardiomyocyte differentiation of anterior heart field progenitors

2010 ◽  
Vol 123 (18) ◽  
pp. e1-e1 ◽  
Author(s):  
L. Tirosh-Finkel ◽  
A. Zeisel ◽  
M. Brodt-Ivenshitz ◽  
A. Shamai ◽  
Z. Yao ◽  
...  
Keyword(s):  
Cardiomyocyte Differentiation ◽  
Fgf Signaling ◽  
Heart Field ◽  
Anterior Heart Field

scholarly journals SORBS2 is a genetic factor contributing to cardiac malformation of 4q deletion syndrome patients

eLife ◽  
2021 ◽  
Vol 10 ◽  
Author(s):  
Fei Liang ◽  
Bo Wang ◽  
Juan Geng ◽  
Guoling You ◽  
Jingjing Fa ◽  
...  
Keyword(s):  
Embryonic Stem ◽  
Stem Cell Differentiation ◽  
Deletion Syndrome ◽  
Marker Genes ◽  
Embryonic Stem Cell Differentiation ◽  
Cardiomyocyte Differentiation ◽  
Mouse Mutants ◽  
Heart Field ◽  
Cardiomyocyte Number ◽  
Molecular Etiology

Chromosome 4q deletion is one of the most frequently detected genomic imbalance events in congenital heart disease (CHD) patients. However, a portion of CHD-associated 4q deletions without known CHD genes suggests unknown CHD genes within these intervals. Here, we have shown that knockdown of SORBS2, a 4q interval gene, disrupted sarcomeric integrity of cardiomyocytes and caused reduced cardiomyocyte number in human embryonic stem cell differentiation model. Molecular analyses revealed decreased expression of second heart field (SHF) marker genes and impaired NOTCH and SHH signaling in SORBS2-knockdown cells. Exogenous SHH rescued SORBS2 knockdown-induced cardiomyocyte differentiation defects. Sorbs2-/- mouse mutants had atrial septal hypoplasia/aplasia or double atrial septum (DAS) derived from impaired posterior SHF with a similar expression alteration. Rare SORBS2 variants were significantly enriched in a cohort of 300 CHD patients. Our findings indicate that SORBS2 is a regulator of SHF development and its variants contribute to CHD pathogenesis. The presence of DAS in Sorbs2-/- hearts reveals the first molecular etiology of this rare anomaly linked to paradoxical thromboembolism.

scholarly journals N-cadherin prevents the premature differentiation of anterior heart field progenitors in the pharyngeal mesodermal microenvironment

Cell Research ◽  
2014 ◽  
Vol 24 (12) ◽  
pp. 1420-1432 ◽  
Author(s):  
Boon-Seng Soh ◽  
Kristina Buac ◽  
Huansheng Xu ◽  
Edward Li ◽  
Shi-Yan Ng ◽  
...  
Keyword(s):  
Heart Field ◽  
Anterior Heart Field

scholarly journals Maternal hyperglycemia impedes second heart field-derived cardiomyocyte differentiation to elevate the risk of congenital heart defects

2021 ◽  
Author(s):  
Sathiyanarayanan Manivannan ◽  
Corrin Mansfield ◽  
Xinmin Zhang ◽  
Karthik M. Kodigepalli ◽  
Uddalak Majumdar ◽  
...  
Keyword(s):  
Congenital Heart ◽  
Heart Defects ◽  
Lineage Tracing ◽  
Ventricular Wall ◽  
Cardiomyocyte Differentiation ◽  
Glucose Levels ◽  
Second Heart Field ◽  
Maternal Hyperglycemia ◽  
Wall Thinning ◽  
Heart Field

Congenital heart disease (CHD) is the most frequently occurring structural malformations of the heart affecting ~1% of live births. Besides genetic predisposition, embryonic exposure to teratogens during pregnancy increases the risk of CHD. However, the dose and cell-type-specific responses to an adverse maternal environment remain poorly defined. Here, we report a dose-response relationship between maternal glucose levels and phenotypic severity of CHD in offspring, using a chemically-induced pregestational diabetes mellitus (PGDM) mouse model. Embryos from dams with low-level maternal hyperglycemia (matHG) displayed trabeculation defects, ventricular wall thinning, and ventricular septal defects (VSD). On the other hand, embryos from dams with high-level matHG display outflow tract malformations, ventricular wall thinning and an increased rate of VSD. Our findings show that increasing levels of matHG exacerbates CHD occurrence and severity in offspring compared to control embryos. We applied single-cell RNA- sequencing to define matHG-related transcriptional differences in E9.5 and E11.5 hearts as comparing to controls. Disease-dependent gene-expression changes were observed in Isl1+ second heart field (SHF) and Tnnt2+ cardiomyocyte subpopulations. Lineage tracing studies in Isl1-Cre; RosamTmG embryonic hearts showed Isl1+-SHF-derived cardiomyocyte differentiation was impaired with matHG. This study highlights the influence of matHG-dosage on cardiac morphogenesis and identifies perturbations in the Isl1-dependent gene-regulatory network that affect SHF-derived cardiomyocyte differentiation contributing to matPGDM-induced CHD.

scholarly journals The right ventricle, outflow tract, and ventricular septum comprise a restricted expression domain within the secondary/anterior heart field

2005 ◽  
Vol 287 (1) ◽  
pp. 134-145 ◽  
Author(s):  
Michael P. Verzi ◽  
David J. McCulley ◽  
Sarah De Val ◽  
Evdokia Dodou ◽  
Brian L. Black
Keyword(s):  
Right Ventricle ◽  
Outflow Tract ◽  
Ventricular Septum ◽  
Expression Domain ◽  
Heart Field ◽  
The Right ◽  
Anterior Heart Field

scholarly journals Hedgehog signaling activates a heterochronic gene regulatory network to control differentiation timing across lineages

2018 ◽  
Author(s):  
Megan Rowton ◽  
Carlos Perez-Cervantes ◽  
Ariel Rydeen ◽  
Suzy Hur ◽  
Jessica Jacobs-Li ◽  
...  
Keyword(s):  
Gene Regulatory Network ◽  
Regulatory Network ◽  
Hedgehog Signaling ◽  
Cardiomyocyte Differentiation ◽  
Cardiac Progenitors ◽  
Second Heart Field ◽  
Heart Field ◽  
Gene Regulatory ◽  
Hh Signaling

SUMMARYHeterochrony, defined as differences in the timing of developmental processes, impacts organ development, homeostasis, and regeneration. The molecular basis of heterochrony in mammalian tissues is poorly understood. We report that Hedgehog signaling activates a heterochronic pathway that controls differentiation timing in multiple lineages. A differentiation trajectory from second heart field cardiac progenitors to first heart field cardiomyocytes was identified by single-cell transcriptional profiling in mouse embryos. A survey of developmental signaling pathways revealed specific enrichment for Hedgehog signaling targets in cardiac progenitors. Removal of Hh signaling caused loss of progenitor and precocious cardiomyocyte differentiation gene expression in the second heart field in vivo. Introduction of active Hh signaling to mESC-derived progenitors, modelled by transient expression of the Hh-dependent transcription factor GLI1, delayed differentiation in cardiac and neural lineages in vitro. A shared GLI1-dependent network in both cardiac and neural progenitors was enriched with FOX family transcription factors. FOXF1, a GLI1 target, was sufficient to delay onset of the cardiomyocyte differentiation program in progenitors, by epigenetic repression of cardiomyocyte-specific enhancers. Removal of active Hh signaling or Foxf1 expression from second heart field progenitors caused precocious cardiac differentiation in vivo, establishing a mechanism for resultant Congenital Heart Disease. Together, these studies suggest that Hedgehog signaling directly activates a gene regulatory network that functions as a heterochronic switch to control differentiation timing across developmental lineages.

scholarly journals Impaired Development of Left Anterior Heart Field by Ectopic Retinoic Acid Causes Transposition of the Great Arteries

2015 ◽  
Vol 4 (5) ◽  
Author(s):  
Mayu Narematsu ◽  
Tatsuya Kamimura ◽  
Toshiyuki Yamagishi ◽  
Mitsuru Fukui ◽  
Yuji Nakajima
Keyword(s):  
Retinoic Acid ◽  
Heart Field ◽  
Anterior Heart Field
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