scholarly journals The Cardiac Neural Crest Cells in Heart Development and Congenital Heart Defects

2021 ◽  
Vol 8 (8) ◽  
pp. 89
Author(s):  
Shannon Erhardt ◽  
Mingjie Zheng ◽  
Xiaolei Zhao ◽  
Tram P. Le ◽  
Tina O. Findley ◽  
...  
Keyword(s):  
Neural Crest ◽  
Signaling Pathways ◽  
Congenital Heart Defects ◽  
Heart Development ◽  
Congenital Heart ◽  
Heart Defects ◽  
Interventricular Septum ◽  
Neural Crest Cells ◽  
Cardiovascular Development ◽  
Cardiac Neural Crest

The neural crest (NC) is a multipotent and temporarily migratory cell population stemming from the dorsal neural tube during vertebrate embryogenesis. Cardiac neural crest cells (NCCs), a specified subpopulation of the NC, are vital for normal cardiovascular development, as they significantly contribute to the pharyngeal arch arteries, the developing cardiac outflow tract (OFT), cardiac valves, and interventricular septum. Various signaling pathways are shown to orchestrate the proper migration, compaction, and differentiation of cardiac NCCs during cardiovascular development. Any loss or dysregulation of signaling pathways in cardiac NCCs can lead to abnormal cardiovascular development during embryogenesis, resulting in abnormalities categorized as congenital heart defects (CHDs). This review focuses on the contributions of cardiac NCCs to cardiovascular formation, discusses cardiac defects caused by a disruption of various regulatory factors, and summarizes the role of multiple signaling pathways during embryonic development. A better understanding of the cardiac NC and its vast regulatory network will provide a deeper insight into the mechanisms of the associated abnormalities, leading to potential therapeutic advancements.

scholarly journals Epigenetic Regulation of Cardiac Neural Crest Cells

2021 ◽  
Vol 9 ◽  
Author(s):  
Shun Yan ◽  
Jin Lu ◽  
Kai Jiao
Keyword(s):  
Neural Crest ◽  
Epigenetic Regulation ◽  
Heart Development ◽  
Congenital Heart ◽  
Heart Diseases ◽  
Heart Defects ◽  
Neural Crest Cells ◽  
Abnormal Development ◽  
Cardiac Neural Crest ◽  
Epigenetic Regulators

The cardiac neural crest cells (cNCCs) is a transient, migratory cell population that contribute to the formation of major arteries and the septa and valves of the heart. Abnormal development of cNCCs leads to a spectrum of congenital heart defects that mainly affect the outflow region of the hearts. Signaling molecules and transcription factors are the best studied regulatory events controlling cNCC development. In recent years, however, accumulated evidence supports that epigenetic regulation also plays an important role in cNCC development. Here, we summarize the functions of epigenetic regulators during cNCC development as well as cNCC related cardiovascular defects. These factors include ATP-dependent chromatin remodeling factors, histone modifiers and DNA methylation modulators. In many cases, mutations in the genes encoding these factors are known to cause inborn heart diseases. A better understanding of epigenetic regulators, their activities and their roles during heart development will ultimately contribute to the development of new clinical applications for patients with congenital heart disease.

scholarly journals Mutation of LRP1 in cardiac neural crest cells causes congenital heart defects by perturbing outflow lengthening

2020 ◽  
Vol 3 (1) ◽  
Author(s):  
Jiuann-Huey I. Lin ◽  
Timothy N. Feinstein ◽  
Anupma Jha ◽  
Jacob T. McCleary ◽  
Juan Xu ◽  
...  
Keyword(s):  
Neural Crest ◽  
Congenital Heart Defects ◽  
Congenital Heart ◽  
Heart Defects ◽  
Neural Crest Cells ◽  
Cardiac Neural Crest

Exposure of neural crest cells to elevated glucose leads to congenital heart defects, an effect that can be prevented by N-acetylcysteine

2007 ◽  
Vol 79 (3) ◽  
pp. 231-235 ◽  
Author(s):  
Pauline A. M. Roest ◽  
Liesbeth van Iperen ◽  
Shirley Vis ◽  
Lambertus J. Wisse ◽  
Rob E. Poelmann ◽  
...  
Keyword(s):  
Neural Crest ◽  
Congenital Heart Defects ◽  
Congenital Heart ◽  
Heart Defects ◽  
Neural Crest Cells ◽  
Elevated Glucose

Abstract 939: Galpha-i Signaling in Neural Crest Cells is Required for Normal Migration of Cardiac Neural Crest Cells, Cardiac Development, and Survival

Circulation ◽  
2007 ◽  
Vol 116 (suppl_16) ◽  
Author(s):  
Kathleen M Ruppel ◽  
Hiroshi Kataoka ◽  
Michelle Iwaki ◽  
Ivo Cornelissen ◽  
Shaun R Coughlin
Keyword(s):  
Neural Crest ◽  
Signaling Pathways ◽  
Aortic Arch ◽  
G Protein ◽  
Heart Defects ◽  
Neural Crest Cells ◽  
Outflow Tract ◽  
Potential Candidate ◽  
Dependent Manner ◽  
Cardiovascular Development

G protein coupled receptors (GPCRs) have long been known to play crucial roles in transducing environmental signals to the adult cardiovascular system. In recent years, the roles of G protein-mediated signaling pathways in orchestrating the interactions of different tissues during cardiovascular development have become increasingly evident. To analyze the role of G protein signaling pathways in vivo we have generated mice where the function of the heterotrimeric G alpha subunit Gai can be ablated in a cell type specific manner utilizing the Cre-loxP system. We have mated these mice to two different neural crest-specific Cre lines in order to probe the effects of loss of Gai mediated signaling on the ability of neural crest cells (NCC) to contribute to the developing outflow tract and aortic arch arteries. METHODS: We have generated mice that express the Gai-inhibiting pertussis toxin S1 subunit (PTX) from the ROSA26 locus in a Cre recombination dependent manner (ROSA-PTX mice). These were mated to mice expressing either the Wnt1 Cre or P0 Cre transgene. Wnt1Cre is active in both premigratory and migratory NCC, whereas P0Cre is active only in migratory NCC and their derivatives. RESULTS: P0Cre-ROSA-PTX mice were normal at birth and demonstrated no structural heart defects. In contrast, Wnt1Cre-ROSA-PTX mice were present in normal numbers at late gestation but died perinatally due in part to cardiac outflow tract defects. Excision reporter and in situ hybridization studies suggest this is secondary to a delay/blockage of cardiac NCC migration into the developing outflow tract. NCC migration into the pharyngeal arches was unaffected in these mice and no craniofacial, thymic, or aortic arch abnormalities were observed. CONCLUSIONS: These results indicate that Gai-mediated signaling is required in premigratory or early migratory cardiac NCC for normal development of the outflow tract. In contrast, endothelin A receptor knockout mice (currently the only GPCR knock out with a neural crest phenotype) are thought to exhibit defects of postmigratory NCC function. RNA profiling of NCC for GPCRs involved in this Gai-dependent pathway has revealed several potential candidate receptors, including orphan receptors. Further analysis of these receptors is underway.

scholarly journals Connecting teratogen-induced congenital heart defects to neural crest cells and their effect on cardiac function

2014 ◽  
Vol 102 (3) ◽  
pp. 227-250 ◽  
Author(s):  
Ganga H. Karunamuni ◽  
Pei Ma ◽  
Shi Gu ◽  
Andrew M. Rollins ◽  
Michael W. Jenkins ◽  
...  
Keyword(s):  
Cardiac Function ◽  
Neural Crest ◽  
Congenital Heart Defects ◽  
Congenital Heart ◽  
Heart Defects ◽  
Neural Crest Cells

scholarly journals Endocytic Protein Defects in the Neural Crest Cell Lineage and Its Pathway Are Associated with Congenital Heart Defects

2021 ◽  
Vol 22 (16) ◽  
pp. 8816
Author(s):  
Angelo B. Arrigo ◽  
Jiuann-Huey Ivy Lin
Keyword(s):  
Neural Crest ◽  
Congenital Heart Defects ◽  
Congenital Heart ◽  
Cardiac Development ◽  
Heart Defects ◽  
Cell Lineage ◽  
Neural Crest Cell ◽  
Neural Crest Cells ◽  
Endocytic Trafficking ◽  
Cardiac Phenotype

Endocytic trafficking is an under-appreciated pathway in cardiac development. Several genes related to endocytic trafficking have been uncovered in a mutagenic ENU screen, in which mutations led to congenital heart defects (CHDs). In this article, we review the relationship between these genes (including LRP1 and LRP2) and cardiac neural crest cells (CNCCs) during cardiac development. Mice with an ENU-induced Lrp1 mutation exhibit a spectrum of CHDs. Conditional deletion using a floxed Lrp1 allele with different Cre drivers showed that targeting neural crest cells with Wnt1-Cre expression replicated the full cardiac phenotypes of the ENU-induced Lrp1 mutation. In addition, LRP1 function in CNCCs is required for normal OFT lengthening and survival/expansion of the cushion mesenchyme, with other cell lineages along the NCC migratory path playing an additional role. Mice with an ENU-induced and targeted Lrp2 mutation demonstrated the cardiac phenotype of common arterial trunk (CAT). Although there is no impact on CNCCs in Lrp2 mutants, the loss of LRP2 results in the depletion of sonic hedgehog (SHH)-dependent cells in the second heart field. SHH is known to be crucial for CNCC survival and proliferation, which suggests LRP2 has a non-autonomous role in CNCCs. In this article, other endocytic trafficking proteins that are associated with CHDs that may play roles in the NCC pathway during development, such as AP1B1, AP2B1, FUZ, MYH10, and HECTD1, are reviewed.

scholarly journals Focused Strategies for Defining the Genetic Architecture of Congenital Heart Defects

Genes ◽  
2021 ◽  
Vol 12 (6) ◽  
pp. 827
Author(s):  
Lisa J. Martin ◽  
D Woodrow Benson
Keyword(s):  
Genetic Variation ◽  
Congenital Heart Defects ◽  
Heart Development ◽  
Genetic Architecture ◽  
Congenital Heart ◽  
Rare Variants ◽  
Heart Defects ◽  
Genetic Origin ◽  
Genetic Studies ◽  
The Ideal

Congenital heart defects (CHD) are malformations present at birth that occur during heart development. Increasing evidence supports a genetic origin of CHD, but in the process important challenges have been identified. This review begins with information about CHD and the importance of detailed phenotyping of study subjects. To facilitate appropriate genetic study design, we review DNA structure, genetic variation in the human genome and tools to identify the genetic variation of interest. Analytic approaches powered for both common and rare variants are assessed. While the ideal outcome of genetic studies is to identify variants that have a causal role, a more realistic goal for genetic analytics is to identify variants in specific genes that influence the occurrence of a phenotype and which provide keys to open biologic doors that inform how the genetic variants modulate heart development. It has never been truer that good genetic studies start with good planning. Continued progress in unraveling the genetic underpinnings of CHD will require multidisciplinary collaboration between geneticists, quantitative scientists, clinicians, and developmental biologists.

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