Myocardin-related transcription factor B is required in cardiac neural crest for smooth muscle differentiation and cardiovascular development

Li, Jian; Zhu, Xiaohong; Chen, Mary; Cheng, Lan; Zhou, Deying; Lü, Min; Du, Kevin; Epstein, Jonathan A.; Parmacek, Michael S.

doi:10.1073/pnas.0503741102

Cited by 132 publications

(136 citation statements)

References 27 publications

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“…Consistent with previously reported studies (Wang et al, 2002;Li et al, 2005), full-length MRTF-B was able to activate both promoters. The truncated molecule with the ␤geo fusion molecule by itself had no transcriptional activity ( Fig.…”

Section: Mutant Micesupporting

confidence: 92%

“…To further investigate the function of MRTF-B, we analyzed a mouse mutant for MRTF-B generated by insertional mutagenesis. Other gene-trap models of MRTF-B displayed perinatal lethality (Skarnes et al, 1992;Li et al, 2005). Germ-line knockout of MRTF-B resulted in earlier lethality at E13.5 that is characterized by cardiac and branchial arch defects (Oh et al, 2005).…”

Section: Introductionmentioning

confidence: 99%

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Myocardin‐related transcription factor B is required for normal mouse vascular development and smooth muscle gene expression

Wei

Che

Chen

2006

Developmental Dynamics

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Section: Mutant Micesupporting

confidence: 92%

Section: Introductionmentioning

confidence: 99%

Myocardin‐related transcription factor B is required for normal mouse vascular development and smooth muscle gene expression

Wei

Che

Chen

2006

Developmental Dynamics

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“…Gene trapping has provided thousands of new genetic models, the majority of which emulate their targeted deletional mutant counterparts. However, a substantial number of gene trap models produce some level of wild type mRNA in homozygotes carrying the gene trap [40][41][42]. Nonetheless, hypomorphic models may prove useful, especially if targeted deletion of a gene causes embryonic lethality.…”

Section: Discussionmentioning

confidence: 99%

Metabolic derangement of methionine and folate metabolism in mice deficient in methionine synthase reductase

Elmore

Leclerc

et al. 2007

Molecular Genetics and Metabolism

118

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Hyperhomocyst(e)inemia is a metabolic derangement that is linked to the distribution of folate pools, which provide one-carbon units for biosynthesis of purines and thymidylate and for remethylation of homocysteine to form methionine. In humans, methionine synthase deficiency results in the accumulation of methyltetrahydrofolate at the expense of folate derivatives required for purine and thymidylate biosynthesis. Complete ablation of methionine synthase activity in mice results in embryonic lethality. Other mouse models for hyperhomocyst(e)inemia have normal or reduced levels of methyltetrahydrofolate and are not embryonic lethal, although they have decreased ratios of AdoMet/AdoHcy and impaired methylation. We have constructed a mouse model with a gene trap insertion in the Mtrr gene specifying methionine synthase reductase, an enzyme essential for the activity of methionine synthase. This model is a hypomorph, with reduced methionine synthase reductase activity, thus avoiding the lethality associated with the absence of methionine synthase activity. Mtrr gt/gt mice have increased plasma homocyst(e)ine, decreased plasma methionine, and increased tissue methyltetrahydrofolate. Unexpectedly, Mtrr gt/gt mice do not show decreases in the AdoMet/AdoHcy ratio in most tissues. The different metabolite profiles in the various genetic mouse models for hyperhomocysteinemia may be useful in understanding biological effects of elevated homocyst(e)ine.

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“…While all 3 MRTFs transduce cytoskeletal signals to the nucleus, it is noteworthy that myocardin is constitutively nuclear, while MRTF-A and MRTF-B translocate between the cytoplasm and the nucleus (27,28). Mice harboring null or hypomorphic mutations in MRTF-B exhibit a spectrum of cardiovascular patterning defects, recapitulating common forms of congenital heart disease observed in humans (29)(30)(31). These patterning defects are attributable to a block in differentiation of cardiac neural crest cells into vascular SMCs.…”

Section: Introductionmentioning

confidence: 97%

Myocardin regulates expression of contractile genes in smooth muscle cells and is required for closure of the ductus arteriosus in mice

Huang¹,

Cheng²,

Li³

et al. 2008

J. Clin. Invest.

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114

133

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Myocardin (Myocd) is a potent transcriptional coactivator that has been implicated in cardiovascular development and adaptation of the cardiovascular system to hemodynamic stress. To determine the function of myocardin in the developing cardiovascular system, Myocd F/F /Wnt1-Cre + and Myocd F/F /Pax3-Cre + mice were generated in which the myocardin gene was selectively ablated in neural crest-derived SMCs populating the cardiac outflow tract and great arteries. Both Myocd F/F /Wnt1-Cre + and Myocd F/F /Pax3-Cre + mutant mice survived to birth, but died prior to postnatal day 3 from patent ductus arteriosus (PDA). Neural crest-derived SMCs populating the ductus arteriosus (DA) and great arteries exhibited a cell autonomous block in expression of myocardin-regulated genes encoding SMC-restricted contractile proteins. Moreover, Myocd-deficient vascular SMCs populating the DA exhibited ultrastructural features generally associated with the SMC synthetic, rather than contractile, phenotype. Consistent with these findings, ablation of the Myocd gene in primary aortic SMCs harvested from Myocd conditional mutant mice caused a dramatic decrease in SMC contractile protein expression. Taken together, these data demonstrate that myocardin regulates expression of genes required for the contractile phenotype in neural crest-derived SMCs and provide new insights into the molecular and genetic programs that may underlie PDA.

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Myocardin-related transcription factor B is required in cardiac neural crest for smooth muscle differentiation and cardiovascular development

Abstract: congenital heart disease ͉ myocardin ͉ heart ͉ angiogenesis

Cited by 132 publications

References 27 publications

Myocardin‐related transcription factor B is required for normal mouse vascular development and smooth muscle gene expression

Myocardin‐related transcription factor B is required for normal mouse vascular development and smooth muscle gene expression

Metabolic derangement of methionine and folate metabolism in mice deficient in methionine synthase reductase

Myocardin regulates expression of contractile genes in smooth muscle cells and is required for closure of the ductus arteriosus in mice

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