Double-Outlet Right Ventricle and Overriding Tricuspid Valve Reflect Disturbances of Looping, Myocardialization, Endocardial Cushion Differentiation, and Apoptosis in TGF-β2–Knockout Mice

@article{Bartram2001DoubleOutletRV,
  title={Double-Outlet Right Ventricle and Overriding Tricuspid Valve Reflect Disturbances of Looping, Myocardialization, Endocardial Cushion Differentiation, and Apoptosis in TGF-$\beta$2–Knockout Mice},
  author={Ulrike Bartram and Dani{\"e}l G M Molin and Lambertus J. Wisse and Azhar Mohamad and L. Philip Sanford and Thomas C. Doetschman and Christian Paul Speer and Robert E. Poelmann and Adriana C. Gittenberger-de Groot},
  journal={Circulation},
  year={2001},
  volume={103},
  pages={2745-2752}
}
Background—Transforming growth factor-β2 (TGF-β2) is a member of a family of growth factors with the potential to modify multiple processes. Mice deficient in the TGF-β2 gene die around birth and show a variety of defects of different organs, including the heart. Methods and Results—We studied the hearts of TGF-β2–null mouse embryos from 11.5 to 18.5 days of gestation to analyze the types of defects and determine which processes of cardiac morphogenesis are affected by the absence of TGF-β2… 
Molecular Pathways and Animal Models of Tetralogy of Fallot and Double Outlet Right Ventricle
TLDR
The heterogeneity of causes converging on alignment defects characterizes the OFT as a hotspot of congenital heart defects.
Morphogenesis of outflow tract rotation during cardiac development: The pulmonary push concept
TLDR
It is postulated that normally the pulmonary trunk and orifice are pushed in a higher and more frontal position relative to the aortic orifice by asymmetric addition of SHF‐myocardium.
Expression patterns of Tgfβ1–3 associate with myocardialisation of the outflow tract and the development of the epicardium and the fibrous heart skeleton
TLDR
The spatiotemporal cardiovascular expression of Tgfβ1–3 supports both specific and complementary functions during cardiovascular development that might explain functional redundancy between the T gfβ‐isoforms.
Conditional inactivation of TGF-β type II receptor in smooth muscle cells and epicardium causes lethal aortic and cardiac defects
TLDR
During mouse development, TGF-β plays an irreplaceable role on the differentiation of the VSMCs in the coronary vessels and the descending thoracic aorta.
Elevated transforming growth factor beta2 enhances apoptosis and contributes to abnormal outflow tract and aortic sac development in retinoic X receptor alpha knockout embryos.
TLDR
The data suggests that elevated levels of TGFbeta2 can contribute to abnormal outflow tract morphogenesis by enhancing apoptosis in the endocardial cushions and promote aortic sac malformations by interfering with the normal development of theAorticopulmonary septum.
Cellular changes in experimental left heart hypoplasia
TLDR
Analysis of cellular changes leading to the profound remodeling of ventricular myocardial architecture in Hypoplastic left heart syndrome suggests that changes in cardiomyocyte proliferation play a significant role in the pathogenesis of HLHS.
Common arterial trunk and ventricular non-compaction in Lrp2 knockout mice indicate a crucial role of LRP2 in cardiac development
TLDR
New light is shed on the role of the second heart field and neural crest cells in outflow tract formation in the mouse embryo and on the underlying signaling mechanisms in which LRP2 is involved during cardiogenesis.
Development of the Right Ventricular Inflow Tract and Moderator Band: A Possible Morphological and Functional Explanation for Mahaim Tachycardia
TLDR
The formation of the right ventricular (RV) inflow tract in relation to the developing cardiac conduction system is studied and a morphological and functional explanation for atriofascicular accessory pathways via the moderator band, underlying Mahaim tachycardia is hypothesized.
Molecular Pathways and Animal Models of Ventricular Septal Defect
TLDR
This chapter describes the formation of the ventricular septum in the normal heart, as well as the molecular mechanisms leading to the four main anatomic types of ventricularSeptal defects: outlet, inlet, muscular, and central perimembranous, resulting from failure of development of the different parts of the vents.
...
...

References

SHOWING 1-10 OF 22 REFERENCES
Developmental remodeling and shortening of the cardiac outflow tract involves myocyte programmed cell death.
TLDR
The results suggest that the elimination of myocytes by programmed cell death is one mechanism by which the outflow tract myocardium remodels to form the proper connection between the ventricular chambers and the appropriate arterial trunks.
Defects in cardiac outflow tract formation and pro-B-lymphocyte expansion in mice lacking Sox-4
TLDR
Using targeted genedisruption, it is found that Sox-4−/− embryos succumb to circulatory failure at day E14, a result of impaired development of the endocardial ridges into the semilunar valves and the outlet portion of the muscular ventricular septum.
RXR alpha deficiency confers genetic susceptibility for aortic sac, conotruncal, atrioventricular cushion, and ventricular muscle defects in mice.
TLDR
The intermediate phenotype of RXRalpha heterozygous embryos documents a gene dosage effect for RXR alpha in maintaining normal cardiac morphogenesis, and some defects in RXRAlpha mutant mice are phenocopies of human congenital heart defects, thereby suggesting that a relative deficiency in RXS alpha or molecules downstream in its signaling pathway may represent congenitalHeart disease-susceptibility genes.
Development of the cardiac conduction tissue in human embryos using HNK-1 antigen expression: possible relevance for understanding of abnormal atrial automaticity.
TLDR
In patients with abnormal atrial automaticity, the distribution of left and right atrial pacemaker foci correspond to areas of the embryonic myocardium that temporarily express the HNK-1 antigen.
A subpopulation of apoptosis-prone cardiac neural crest cells targets to the venous pole: multiple functions in heart development?
TLDR
Because of the perfect timing of the arrival of crest cells, their apoptosis, and a change in electrophysiological behavior of the heart, it is postulate that neural crest cells play a role in the last phase of differentiation of the cardiac conduction system.
Requirement of type III TGF-beta receptor for endocardial cell transformation in the heart.
TLDR
A model where TBRIII localizes transformation in the heart and plays an essential, nonredundant role in TGF-beta signaling is supported.
Transforming growth factor-beta in cardiac ontogeny and adaptation.
TLDR
A truncated form of the type II TGF-beta receptor, created by deletion of the cytoplasmic kinase domain, acts as a dominant suppressor of T GF-beta signal transduction in cultured cardiac muscle cells and may provide a suitable means to establish the functions of TDF-beta in vivo.
TGFbeta2 knockout mice have multiple developmental defects that are non-overlapping with other TGFbeta knockout phenotypes.
TLDR
Targeted disruption of the TGFbeta2 gene was undertaken to determine its essential role in vivo to exhibit perinatal mortality and a wide range of developmental defects for a single gene disruption.
Unilateral vitelline vein ligation alters intracardiac blood flow patterns and morphogenesis in the chick embryo.
TLDR
It is concluded that abnormal intracARDiac blood flow, resulting from hampered venous inflow, may result in serious intracardiac and pharyngeal arch artery malformations comparable to defects observed in embryonic chicken models subjected to neural crest ablation, cervical flexure experiments, and excessive retinoic acid treatment.
...
...