Msx1 and Msx2are required for endothelial-mesenchymal transformation of the atrioventricular cushions and patterning of the atrioventricular myocardium

Chen, Yi Hui; Ishii, Masahiko; Sucov, Henry M.; Maxson, Robert E.

doi:10.1186/1471-213x-8-75

Cited by 83 publications

(85 citation statements)

References 72 publications

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“…The inactivation of Tbx2, either globally or specifically in the developing myocardium, thus results in malformation of the annulus fibrosus and the ectopic expression of chamber genes in the AVC, leading to the formation of ectopic conductive AV pathways, reminiscent of the situation observed in Wolff-Parkinson-White syndrome of ventricular pre-excitation (Aanhaanen et al, 2011). Tbx2 and Tbx3 interact with the musclesegment homeobox transcription factor Msx2, which is expressed in the AVC, to suppress the expression of Cx43 directly (Boogerd et al, 2008;Chen et al, 2008). They also compete with Tbx5 both for binding to T-box elements in target genes, such as Nppa and Cx40 (Hoogaars et al, 2004;van den Boogaard et al, 2012) , and for interaction with Nkx2-5 to repress Nppa in the AVC (Habets et al, 2002).…”

Section: Transcriptional Regulation Of Avc and Avn Developmentmentioning

confidence: 99%

The formation and function of the cardiac conduction system

2016

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The cardiac conduction system (CCS) consists of distinctive components that initiate and conduct the electrical impulse required for the coordinated contraction of the cardiac chambers. CCS development involves complex regulatory networks that act in stage-, tissue-and dose-dependent manners, and recent findings indicate that the activity of these networks is sensitive to common genetic variants associated with cardiac arrhythmias. Here, we review how these findings have provided novel insights into the regulatory mechanisms and transcriptional networks underlying CCS formation and function.

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Section: Transcriptional Regulation Of Avc and Avn Developmentmentioning

confidence: 99%

The formation and function of the cardiac conduction system

2016

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“…103 Its function and ability to form a complex with Tbx2 and Tbx3 that represses Cx43 expression render Msx2 a possible component of the regulatory pathway controlling AVC for-mation. 104,105 Nevertheless, mice that are deficient in Msx2 do not display conduction defects. 106 Nkx2.5 and Tbx5 are broadly expressed in the embryonic heart, with Tbx5 displaying a more restricted caudocranial graded pattern of expression that is maintained in the atria and AV conduction system.…”

Section: T-box Factors and Nkx25 In Avc Developmentmentioning

confidence: 99%

Development of the Pacemaker Tissues of the Heart

Christoffels

Smits

Kispert

et al. 2010

Circulation Research

261

241

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Pacemaker and conduction system myocytes play crucial roles in initiating and regulating the contraction of the cardiac chambers. Genetic defects, acquired diseases, and aging cause dysfunction of the pacemaker and conduction tissues, emphasizing the clinical necessity to understand the molecular and cellular mechanisms of their development and homeostasis. Although all cardiac myocytes of the developing heart initially possess pacemaker properties, the majority differentiates into working myocardium. Only small populations of embryonic myocytes will form the sinus node and the atrioventricular node and bundle. Recent efforts have revealed that the development of these nodal regions is achieved by highly localized suppression of working muscle differentiation, and have identified transcriptional repressors that mediate this process. This review will summarize and reflect new experimental findings on the cellular origin and the molecular control of differentiation and morphogenesis of the pacemaker tissues of the heart. It will also shed light on the etiology of inborn and acquired errors of nodal tissues. (Circ Res. 2010;106:240-254.)Key Words: conduction system Ⅲ pacemaker Ⅲ sinus venosus Ⅲ atrioventricular canal Ⅲ development T he contractions of the heart are initiated and coordinated by electric signals from pacemaker tissues. At the entrance of the right atrium, sinus node (sinoatrial node [SAN]) myocytes generate the impulse to activate the atrial myocardium. After rapid propagation through the atria, the impulse is delayed in the atrioventricular node (AVN) and further propagated to the fast-conducting atrioventricular bundle (AVB), bundle branches (BB), and Purkinje fiber network, from which the mass of the ventricular working myocardium is activated. The components of the conduction system contain cardiomyocytes with pacemaker activity and other specific nodal properties that discriminate them from atrial and ventricular working myocardium (Figure 1). The SAN serves as the primary pacemaker, whereas the AVN and ventricular conduction system act as secondary (accessory) pacemakers to secure Original

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“…Bone morphogenetic protein 2 (Bmp2) is expressed in the AV canal myocardium progenitors in the early heart tube, in which it stimulates the expression of T-box 2 (Tbx2) (15), a T-box factor required for the development of the AV canal (16)(17)(18). Repressors Tbx3 and Msx2, Notch signaling, and Hey transcription factors further establish the AV canal phenotype (19)(20)(21)(22). Other factors involved in formation and regulation of gene expression of the AV canal and AV node include the more broadly expressed transcription factors Nkx2.5, Gata4, and Tbx5, which interact or compete with the localized repressors (16,(23)(24)(25)(26)(27).…”

Section: Introductionmentioning

confidence: 99%