Connexin43 deficiency causes dysregulation of coronary vasculogenesis

Walker, Diana L.; Vacha, Scott; Kirby, Margaret L.; Lo, Cecilia

doi:10.1016/j.ydbio.2005.06.004

Cited by 68 publications

(66 citation statements)

References 91 publications

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“…(C,D). This mutant heart also has a blistering appearance of the right ventricular lateral wall, possibly consistent with subepicardial coronary plexuses described in the germline Cx43-null heart (arrows, E) (Walker et al, 2005). (F-H) Another neonatal Cx43-PCKO heart has dual right coronary ostia.…”

Section: Research Articlesupporting

confidence: 70%

“…Previous work by others has established that Cx43 plays an important role in coronary artery development (Li et al, 2002;Walker et al, 2005). Our study suggests that the effect of Cx43 on coronary patterning is mediated through its expression in the NC.…”

Section: Research Articlesupporting

confidence: 65%

“…Cell density in the infundibular regions of Cx43-PCKO hearts was 2067 RESEARCH ARTICLE Neuroepithelial Cx43 influences heart development 4.5±1.6 cells/10 m 2 (n=4), compared with a density of 3.5±0.7 cells/10 m 2 (n=5) in controls. Although this difference was not statistically significant, in conjunction with upregulation of genes specific for vascular smooth muscle cells, endothelial cells and fibroblasts in Cx43 KO infundibular tissue (Walker et al, 2005), these data suggest an altered cellular composition of the mutant RVOTs. Infundibular bulging may result from such a change in cellular composition, which makes the RVOT unable to withstand increasing myocardial wall stress as development progresses.…”

Section: Research Articlementioning

confidence: 57%

“…Wnt1-Cre-mediated loss of Cx43 is associated with coronary anomalies Coronary artery malformations have been described in both heterozygous and homozygous germline Cx43-null mice (Li et al, 2002;Walker et al, 2005). We investigated whether targeted loss of Cx43 using the Cx43-WCKO strategy might influence coronary patterning.…”

Section: Nc-specific Loss Of Cx43 Expression In the Cx43-wcko Linementioning

confidence: 99%

“…Genetic models including those with mutations in or knockouts of Pax3, neurotrophin 3/TrkC, TGF␤ receptor type II, BMP4, BMP receptor IA, endothelin 1 and combinations of retinoic acid receptors (Choudhary et al, 2006;Donovan et al, 1996;Epstein et al, 2000;Kurihara et al, 1995;Liu et al, 2004;Mendelsohn et al, 1994;Stottmann et al, 2004;Youn et al, 2003) commonly cause OFT septation defects similar to those resulting from chick NC ablation. Thus, during development, Cx43 may be required in tissues that contribute to heart formation other than or in addition to the CNC (Li et al, 2002;Walker et al, 2005).…”

Section: Introductionmentioning

confidence: 99%

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Distinct cardiac malformations caused by absence of connexin 43 in the neural crest and in the non-crest neural tube

Liu

Schneider

et al. 2006

Development

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Connexin 43 (Cx43) is expressed in the embryonic heart, cardiac neural crest (CNC) and neural tube, and germline knockout (KO) of Cx43 results in aberrant cardiac outflow tract (OFT) formation and abnormal coronary deployment. Prior studies suggest a vital role for CNC expression of Cx43 in heart development. Surprisingly, we found that conditional knockout (CKO) of Cx43 in the dorsal neural tube and CNC mediated by Wnt1-Cre failed to recapitulate the Cx43-null OFT phenotype, although coronary vasculature was abnormal in this mutant line. A broader CKO mediated by P3pro (Pax3)-Cre, involving both ventral and dorsal aspects of the thoracic neural tube and CNC, resulted in infundibular bulging and coronary anomalies similar to those seen in germline Cx43-null hearts. P3pro-Cre-mediated loss of Cx43 in the neural tube was characterized by a late phase of cellular delamination from the dorsal and lateral neural tube, a markedly increased abundance of neuroepithelium-derived cells outside of the neural tube and an excess of such cells infiltrating the heart and infundibulum. Thus, expression of Cx43 in the CNC is crucial for normal coronary deployment, but Cx43 is not required in the CNC for normal OFT morphogenesis. Rather, this study suggests a novel function for Cx43 in which Cx43 acts through non-crest neuroepithelial cells to suppress cellular delamination from the neural tube and thereby preserve normal OFT development.

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Section: Research Articlesupporting

confidence: 70%

Section: Research Articlesupporting

confidence: 65%

Section: Research Articlementioning

confidence: 57%

Section: Nc-specific Loss Of Cx43 Expression In the Cx43-wcko Linementioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

Distinct cardiac malformations caused by absence of connexin 43 in the neural crest and in the non-crest neural tube

Liu

Schneider

et al. 2006

Development

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Coronary Anomalies in Mice With Congenital Heart Defects

Tomanek

2014

The Anatomical Record

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Background: Coronary anomalies are frequently associated with congenital cardiac defects. Accordingly, we tested the hypothesis that the development of the tunica media of coronary arteries/arterioles is compromised in mice with cardiac defects of the outflow tract (persistent truncus arteriosus, double outlet right ventricle and transposition of the great arteries) by studying hearts of G7-9 generation mice bred from mutagenized mice caused by N-ethyl-N-nitrosourea. Mice were studied at embryonic days E16.5, E17.5, and postnatal days 1 and 11. Data were based on immunohistochemistry of serial sections. Results: In 21 of 24 mice with outflow tract defects, the development of smooth muscle in arteries and arterioles was retarded; most commonly arterioles had an incomplete layer of smooth muscle or in a few instances, lacked a tunica media. In this model, an absence of a coronary ostium occurred in only 2 mice, indicating that the mechanisms underlying the formation of coronary ostia and the recruitment and differentiation of vascular smooth muscle differ. Coronary fistulas were present in 20% and dilated vessels in 30% of the hearts with cardiac defects. Conclusions: The data suggest that vascular smooth muscle recruitment and differentiation are not necessarily linked to other coronary anomalies, such as absence of a main coronary artery or branching patterns. Anat Rec, 298:408-417, 2015. V C 2014 Wiley Periodicals, Inc.

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