Molecular Embryogenesis of the Heart

2002 ◽  
Vol 5 (6) ◽  
pp. 516-543 ◽  
Author(s):  
Margaret L. Kirby ◽  
Karen L. Waldo
Keyword(s):  
Molecular Genetic ◽  
Heart Tube ◽  
Molecular Control ◽  
Complex Process ◽  
Molecular Genetic Basis ◽  
Heart Field ◽  
Endocardial Cell ◽  
Heart Fields ◽  
Secondary Heart Field ◽  
Myocardial Differentiation

Development of the heart is a complex process involving primary and secondary heart fields that are set aside to generate myocardial and endocardial cell lineages. The molecular inductions that occur in the primary heart field appear to be recapitulated in induction and myocardial differentiation of the secondary heart field, which adds the conotruncal segments to the primary heart tube. While much is now known about the initial steps and factors involved in induction of myocardial differentiation, little is known about induction of endocardial development. Many of the genes expressed by nascent myocardial cells, which then become committed to a specific heart segment, have been identified and studied. In addition to the heart fields, several other “extracardiac” cell populations contribute to the fully functional mature heart. Less is known about the genetic programs of extracardiac cells as they enter the heart and take part in cardiogenesis. The molecular/genetic basis of many congenital cardiac defects has been elucidated in recent years as a result of new insights into the molecular control of developmental events.

scholarly journals Conotruncal myocardium arises from a secondary heart field

Development ◽  
2001 ◽  
Vol 128 (16) ◽  
pp. 3179-3188 ◽  
Author(s):  
Karen L. Waldo ◽  
Donna H. Kumiski ◽  
Kathleen T. Wallis ◽  
Harriett A. Stadt ◽  
Mary. R. Hutson ◽  
...  
Keyword(s):  
Heart Development ◽  
Outflow Tract ◽  
Heart Tube ◽  
In Ovo ◽  
Atrioventricular Canal ◽  
Lateral Plate ◽  
Heart Field ◽  
Dorsal Mesocardium ◽  
Heart Fields ◽  
Secondary Heart Field

The primary heart tube is an endocardial tube, ensheathed by myocardial cells, that develops from bilateral primary heart fields located in the lateral plate mesoderm. Earlier mapping studies of the heart fields performed in whole embryo cultures indicate that all of the myocardium of the developed heart originates from the primary heart fields. In contrast, marking experiments in ovo suggest that the atrioventricular canal, atria and conotruncus are added secondarily to the straight heart tube during looping. The results we present resolve this issue by showing that the heart tube elongates during looping, concomitant with accretion of new myocardium. The atria are added progressively from the caudal primary heart fields bilaterally, while the myocardium of the conotruncus is elongated from a midline secondary heart field of splanchnic mesoderm beneath the floor of the foregut. Cells in the secondary heart field express Nkx2.5 and Gata-4, as do the cells of the primary heart fields. Induction of myocardium appears to be unnecessary at the inflow pole, while it occurs at the outflow pole of the heart. Accretion of myocardium at the junction of the inflow myocardium with dorsal mesocardium is completed at stage 12 and later (stage 18) from the secondary heart field just caudal to the outflow tract. Induction of myocardium appears to move in a caudal direction as the outflow tract translocates caudally relative to the pharyngeal arches. As the cells in the secondary heart field begin to move into the outflow or inflow myocardium,they express HNK-1 initially and then MF-20, a marker for myosin heavy chain. FGF-8 and BMP-2 are present in the ventral pharynx and secondary heart field/outflow myocardium, respectively, and appear to effect induction of the cells in a manner that mimics induction of the primary myocardium from the primary heart fields. Neither FGF-8 nor BMP-2 is present as inflow myocardium is added from the primary heart fields. The addition of a secondary myocardium to the primary heart tube provides a new framework for understanding several null mutations in mice that cause defective heart development.

scholarly journals STAG2 cohesin is essential for heart morphogenesis

2019 ◽  
Author(s):  
M. De Koninck ◽  
E. Lapi ◽  
C. Badia-Careaga ◽  
I. Cossio ◽  
D. Giménez-Llorente ◽  
...  
Keyword(s):  
Heart Defects ◽  
Germline Mutations ◽  
Global Developmental Delay ◽  
Histopathological Analysis ◽  
Compelling Evidence ◽  
Heart Tube ◽  
Embryonic Fibroblasts ◽  
Heart Field ◽  
Secondary Heart Field

AbstractThe distinct functions of cohesin complexes carrying STAG1 or STAG2 need to be unraveled. STAG2 is commonly mutated in cancer and germline mutations have been identified in cohesinopathy patients. To better understand the underlying pathogenic mechanisms, we here report the consequence of Stag2 ablation in mice. STAG2 is largely dispensable in adults and its tissue-wide inactivation does not lead to tumors but reduces fitness and affects both hematopoiesis and intestinal homeostasis. STAG2 is also dispensable for murine embryonic fibroblasts in vitro. In contrast, null embryos die by mid gestation showing global developmental delay and heart defects. Histopathological analysis and RNA-sequencing unveiled that STAG2 is required both for proliferation and regulation of cardiac transcriptional programs and in its absence, secondary heart field progenitors fail to enter the heart tube. These results provide compelling evidence on cell- and tissue-specific roles of the two cohesin complexes and how their dysfunction contributes to disease.

scholarly journals A Role for the Cytoskeleton in Heart Looping

2007 ◽  
Vol 7 ◽  
pp. 280-298 ◽  
Author(s):  
Kersti K. Linask ◽  
Michael VanAuker
Keyword(s):  
Heart Development ◽  
Cell Biology ◽  
Heart Defects ◽  
Heart Tube ◽  
Second Heart Field ◽  
The Past ◽  
Complex Process ◽  
Nonmuscle Myosin Ii ◽  
Heart Looping ◽  
Heart Field

Over the past 10 years, key genes involved in specification of left-right laterality pathways in the embryo have been defined. The read-out for misexpression of laterality genes is usually the direction of heart looping. The question of how dextral looping direction occurred mechanistically and how the heart tube bends remains unknown. It is becoming clear from our experiments and those of others that left-right differences in cell proliferation in the second heart field (anterior heart field) drives the dextral direction. Evidence is accumulating that the cytoskeleton is at the center of laterality, and the bending and rotational forces associated with heart looping. If laterality pathways are modulated upstream, the cytoskeleton, including nonmuscle myosin II (NMHC-II), is altered downstream within the cardiomyocytes, leading to looping abnormalities. The cytoskeleton is associated with important mechanosensing and signaling pathways in cell biology and development. The initiation of blood flow during the looping period and the inherent stresses associated with increasing volumes of blood flowing into the heart may help to potentiate the process. In recent years, the steps involved in this central and complex process of heart development that is the basis of numerous congenital heart defects are being unraveled.

scholarly journals Outflow Tract Formation—Embryonic Origins of Conotruncal Congenital Heart Disease

2021 ◽  
Vol 8 (4) ◽  
pp. 42
Author(s):  
Sonia Stefanovic ◽  
Heather C. Etchevers ◽  
Stéphane Zaffran
Keyword(s):  
Congenital Heart ◽  
Cardiac Development ◽  
Heart Defects ◽  
Dynamic Structure ◽  
Cell Types ◽  
Outflow Tract ◽  
Heart Tube ◽  
Heart Field ◽  
Multiple Cell ◽  
The Many

Anomalies in the cardiac outflow tract (OFT) are among the most frequent congenital heart defects (CHDs). During embryogenesis, the cardiac OFT is a dynamic structure at the arterial pole of the heart. Heart tube elongation occurs by addition of cells from pharyngeal, splanchnic mesoderm to both ends. These progenitor cells, termed the second heart field (SHF), were first identified twenty years ago as essential to the growth of the forming heart tube and major contributors to the OFT. Perturbation of SHF development results in common forms of CHDs, including anomalies of the great arteries. OFT development also depends on paracrine interactions between multiple cell types, including myocardial, endocardial and neural crest lineages. In this publication, dedicated to Professor Andriana Gittenberger-De Groot and her contributions to the field of cardiac development and CHDs, we review some of her pioneering studies of OFT development with particular interest in the diverse origins of the many cell types that contribute to the OFT. We also discuss the clinical implications of selected key findings for our understanding of the etiology of CHDs and particularly OFT malformations.

scholarly journals Zebrafish cardiac development requires a conserved secondary heart field

Development ◽  
2011 ◽  
Vol 138 (11) ◽  
pp. 2389-2398 ◽  
Author(s):  
D. Hami ◽  
A. C. Grimes ◽  
H.-J. Tsai ◽  
M. L. Kirby
Keyword(s):  
Cardiac Development ◽  
Heart Field ◽  
Secondary Heart Field

scholarly journals The Molecular-Genetic Basis of Functional Hyperandrogenism and the Polycystic Ovary Syndrome

2005 ◽  
Vol 26 (2) ◽  
pp. 251-282 ◽  
Author(s):  
Héctor F. Escobar-Morreale ◽  
Manuel Luque-Ramírez ◽  
José L. San Millán
Keyword(s):  
Environmental Factors ◽  
Polycystic Ovary Syndrome ◽  
Diagnostic Criteria ◽  
Genetic Basis ◽  
Polycystic Ovary ◽  
Molecular Genetic ◽  
Ovary Syndrome ◽  
The Metabolic Syndrome ◽  
Molecular Genetic Basis ◽  
Functional Hyperandrogenism

The genetic mechanisms underlying functional hyperandrogenism and the polycystic ovary syndrome (PCOS) remain largely unknown. Given the large number of genetic variants found in association with these disorders, the emerging picture is that of a complex multigenic trait in which environmental influences play an important role in the expression of the hyperandrogenic phenotype. Among others, genomic variants in genes related to the regulation of androgen biosynthesis and function, insulin resistance, and the metabolic syndrome, and proinflammatory genotypes may be involved in the genetic predisposition to functional hyperandrogenism and PCOS. The elucidation of the molecular genetic basis of these disorders has been burdened by the heterogeneity in the diagnostic criteria used to define PCOS, the limited sample size of the studies conducted to date, and the lack of precision in the identification of ethnic and environmental factors that trigger the development of hyperandrogenic disorders. Progress in this area requires adequately sized multicenter collaborative studies after standardization of the diagnostic criteria used to classify hyperandrogenic patients, in whom modifying environmental factors such as ethnicity, diet, and lifestyle are identified with precision. In addition to classic molecular genetic techniques such as linkage analysis in the form of a whole-genome scan and large case-control studies, promising genomic and proteomic approaches will be paramount to our understanding of the pathogenesis of functional hyperandrogenism and PCOS, allowing a more precise prevention, diagnosis, and treatment of these prevalent disorders.

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