Transcriptional Control of Left–Right Patterning in Cardiac Development

  title={Transcriptional Control of Left–Right Patterning in Cardiac Development},
  author={Chiann-Mun Chen and Dominic P Norris and Shoumo Bhattacharya},
  journal={Pediatric Cardiology},
The heart develops from a simple left–right (L–R) symmetrical tube. Through a complex process of looping and remodelling, it becomes a highly L–R asymmetrical organ with distinct asymmetries in both morphology and function. Abnormal cardiac L–R patterning can result in a spectrum of defects that include, dextrocardia (a malposition of the heart to the right), isomerism of the atria (both atria being morphologically right-sided or left-sided), abnormal ventricular topology (e.g. the… 
Congenital heart disease and the specification of left-right asymmetry.
Dnaic1 mutants can achieve situs solitus or inversus even with immotile nodal cilia, which would suggest motile cilia are required for normal heart looping, but heart and visceral organ lateralization is driven by signaling not requiring nodalcilia motility.
Left Right Patterning, Evolution and Cardiac Development
  • Iain M. Dykes
  • Biology, Medicine
    Journal of cardiovascular development and disease
  • 2014
This review discusses the differing mechanisms by which left-right polarity is achieved in the mouse and chick embryos and comment on the evolution of this system, and describes phenotypes associated with the determination of atrial identity and venous connections, looping morphogenesis of the heart tube and asymmetric remodelling of the embryonic branchial arch arterial system.
Morphogenetic control of zebrafish cardiac looping by Bmp signaling
The asymmetric activity of Bmp signaling within the superior atrioventricular canal is essential for normal looping morphogenesis of the zebrafish heart.
Embryological Origins: How Does the Right Ventricle Form
The heart originates from a group of cardiac progenitor cells that form the cardiac tube, which develops into a complex four-chambered beating organ. Several tissues signal to stimulate cardiac
Development of the human heart
The challenge of the newly developed molecular genetic techniques is to unveil the basic gene regulatory networks underlying cardiac morphogenesis.
Unilateral dampening of Bmp activity by nodal generates cardiac left-right asymmetry.
In silico modeling shows that left- right differences in cell motility are sufficient to induce a robust, directional migration of cardiac tissue, and the mechanism underlying the formation of cardiac left-right asymmetry involves Nodal modulating an antimotogenic Bmp activity.
A Requirement for Zic2 in the Regulation of Nodal Expression Underlies the Establishment of Left-Sided Identity
Gene expression analysis showed that the left-determining NODAL-dependent signalling cascade fails to be activated in the LPM, and that the expression of Nodal at the node, which normally triggers this event, is itself defective in these embryos, suggesting a model in which ZIC2 acts at different levels to establish LR asymmetry, promoting both the production of the signal that induces left side identity and the morphogenesis of the cilia that bias its distribution.
On the connective tissue regulator Follistatin-like 1
By deletion of Fstl1 in these tissues it is found that normal expression of FSTl1 is crucial for normal development and a novel signalling role for the endocardium-derived tissue in regulating atrio-ventricular conduction velocity is unveiled.
Growth of the Developing Mouse Heart: a quantitative 3D analysis
Much of our current knowledge on cardiac development is derived from the mouse, a mammalian model permitting molecular analyses along with genetic lineage tracing. Important as the results of these
On the form problem of embryonic heart loops, its geometrical solutions, and a new biophysical concept of cardiac looping.
  • J. Männer
  • Physics, Medicine
    Annals of anatomy = Anatomischer Anzeiger : official organ of the Anatomische Gesellschaft
  • 2013
Analysis of the tendrils of climbing plants disclosed striking resemblance between the configurations of embryonic heart loops and a form motif named helical perversion, which may be the best geometrical solution of the form problem of embryonicHeart loops.


Left-right asymmetry and congenital cardiac defects: getting to the heart of the matter in vertebrate left-right axis determination.
The purpose of this review is to highlight what is presently known about cardiac development and upstream processes of left-right axis determination, and to consider how perturbation of the left- right body plan might ultimately result in particular types of congenital heart defects.
Cited2 is required both for heart morphogenesis and establishment of the left-right axis in mouse development
It is proposed that, in addition to the previously described reduction of cardiac neural crest cells, two other distinct mechanisms contribute to the spectrum of complex cardiac defects in Cited2-null mice; disruption of normal left-right patterning and direct loss of Citation2 expression in cardiac tissues.
A role of the cryptic gene in the correct establishment of the left–right axis
The results provide genetic evidence for a role of cryptic in the signalling cascade that determines left-right asymmetry in vertebrate embryogenesis.
Cited2 controls left-right patterning and heart development through a Nodal-Pitx2c pathway
It is proposed that an abnormal Nodal-Pitx2c pathway represents a unifying mechanism for the cardiovascular malformations observed in Cited2−/− mice, and that such mal Formations may be the sole manifestation of a laterality defect.
The role of Pitx2 during cardiac development. Linking left-right signaling and congenital heart diseases.
Current studies suggest that altered left-right signaling underlies the etiology of several common congenital cardiac malformations.
Node and midline defects are associated with left-right development in Delta1 mutant embryos
It is reported that Notch signalling, which previously had not been implicated in this morphogenetic process, is required for normal left-right determination in mice, and suggested a model, in which Notch signals are required for the proper differentiation of node cells and node morphology.
Conserved requirement for EGF-CFC genes in vertebrate left-right axis formation.
It is proposed that a signaling pathway mediated by Nodal and EGF-CFC activities is essential for transfer of L-R positional information from the node.
Myocardial Pitx2 Differentially Regulates the Left Atrial Identity and Ventricular Asymmetric Remodeling Programs
In situ hybridization analysis and genetic analysis show that myocardial Pitx2 expression delineates the remodeling of the left atrioventricular canal, the inner curvature, the ventral part of the interventricular ring, and the ventrals portion of the right and left ventricle in mouse heart development.
Smad5 is essential for left-right asymmetry in mice.
It is demonstrated that Smad5 mutant embryos have defects in heart looping and embryonic turning which are the first signs of L-R asymmetry in mice, and data suggest thatSmad5 is upstream oflefty-1, nodal, and lefty- 2, and as a consequence also of Pitx2, and Smad 5 is essential for L- R axis determination.
Haemodynamics determined by a genetic programme govern asymmetric development of the aortic arch
The results indicate that haemodynamics, generated by a Pitx2-induced morphological change in the outflow tract, is responsible for the asymmetric remodelling of the great arteries.