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

Wei, Ke; Che, Nam; Chen, Fabian

doi:10.1002/dvdy.21041

Cited by 21 publications

(23 citation statements)

References 36 publications

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“…Disruption of MRTF-B gene results in profound patterning defects of the cardiac outflow tract and great arteries recapitulating common forms of congenital heart disease (29)(30)(31). Like the myocardin conditional mutant mice, the MRTF-B mutants demonstrated a marked decrease in expression of genes encoding SMC contractile proteins (29)(30)(31). However, in contrast to the myocardin conditional mutants, MRTF-B mutant mice exhibit abnormal patterning of the branchial arch arteries as early as E11.0-11.5.…”

Section: Discussionmentioning

confidence: 98%

“…Genetically engineered mice harboring mutations in myocardin, MRTF-A and MRTF-B, respectively, exhibit distinct phenotypes (18). Disruption of MRTF-B gene results in profound patterning defects of the cardiac outflow tract and great arteries recapitulating common forms of congenital heart disease (29)(30)(31). Like the myocardin conditional mutant mice, the MRTF-B mutants demonstrated a marked decrease in expression of genes encoding SMC contractile proteins (29)(30)(31).…”

Section: Discussionmentioning

confidence: 99%

“…MRTF-B mutant mice exhibit a spectrum of cardiovascular patterning defects attributable to a cell autonomous block in differentiation of the cardiac neural crest (29)(30)(31). Given the conserved structure and overlapping patterns of expression of myocardin and MRTF-B in the developing embryo (18), we postulated that Myocd F/F /Wnt1-Cre + pups might exhibit common forms of congenital heart disease attributable to alterations in neural crest patterning of the cardiac outflow tract and great arteries.…”

Section: Conditional Deletion Of Myocardin In Neural Crest-derived Vsmentioning

confidence: 99%

“…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%

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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.

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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Section: Discussionmentioning

confidence: 98%

Section: Discussionmentioning

confidence: 99%

Section: Conditional Deletion Of Myocardin In Neural Crest-derived Vsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 97%

See 2 more Smart Citations

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.

114

133

View full text Add to dashboard Cite

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“…Two lines of genetically engineered mice that harbor loss-offunction mutations in the Mkl2 gene have been described (Li et al, 2005;Oh et al, 2005;Wei et al, 2007). Mice containing an Mkl2 insertional gene trap mutation located between exons 10 and 11 exhibit a hypomorphic phenotype.…”

Section: Introductionmentioning

confidence: 99%

Myocardin-like protein 2 regulates TGFβ signaling in embryonic stem cells and the developing vasculature

Bowens

Cheng

et al. 2012

Development

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SUMMARYThe molecular mechanisms that regulate and coordinate signaling between the extracellular matrix (ECM) and cells contributing to the developing vasculature are complex and poorly understood. Myocardin-like protein 2 (MKL2) is a transcriptional co-activator that in response to RhoA and cytoskeletal actin signals physically associates with serum response factor (SRF), activating a subset of SRF-regulated genes. We now report the discovery of a previously undescribed MKL2/TGF signaling pathway in embryonic stem (ES) cells that is required for maturation and stabilization of the embryonic vasculature.

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Myocardin Marks the Earliest Cardiac Gene Expression and Plays an Important Role in Heart Development

Chen

Wang

et al. 2008

The Anatomical Record

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Myocardin belongs to the SAP domain family of transcription factors and is expressed specifically in cardiac and smooth muscle during embryogenesis and in adulthood. Myocardin functions as a transcriptional coactivator of SRF and is sufficient and necessary for smooth muscle gene expression. However, the in vivo function of myocardin during cardiogenesis is not completely understood. Here we clone myocardin from chick embryonic hearts and show that myocardin protein sequences are highly conserved cross species. Detailed studies of chick myocardin expression reveal that myocardin is expressed in cardiac and smooth muscle lineage during early embryogenesis, similar to that found in mouse. Interestingly, the expression of myocardin in the heart was found enriched in the outflow tract and the sinoatrial segments shortly after the formation of linear heart tube. Such expression pattern is also maintained in later developing embryos, suggesting that myocardin may play a unique role in the formation of those cardiac modules. Similar to its mouse counterpart, chick myocardin is able to activate cardiac and smooth muscle promoter reporter genes and induce smooth muscle gene expression in nonmuscle cells. Ectopic overexpression of myocardin enlarged the embryonic chick heart. Conversely, repression of the endogenous chick myocardin using antisense oligonucleotides or a dominant negative mutant form of myocardin inhibited cardiogenesis. Together, our data place myocardin as one of the earliest cardiac marker genes for cardiogenesis and support the idea that myocardin plays an essential role in cardiac gene expression and cardiogenesis. Anat Rec, 291:1200-1211, 2008. 2008 Key words: myocardin; SRF; heart; cardiac development; gene expression; transcription factor; chick embryosThe heart is the first organ to form during mammalian development (Srivastava and Olson, 2000;Olson, 2002). Several transcription factors have been implicated in activation of cardiac muscle gene expression during cardiomyocyte differentiation (Olson, 2004). NKX2.5, a homeobox protein, is expressed specifically in the heart and has been shown to bind a regulatory element in several cardiac gene control regions (Komuro and Izumo, 1993;Lints et al., 1993;Lyons et al., 1995;Tanaka et al., 1999). MEF2C, a member of myocyte enhance factor-2 (MEF2) family of MADS-box transcription factors, binds to a conserved A/T-rich DNA sequence in the THE ANATOMICAL RECORD 291:1200-1211 (2008 control regions of the majority of cardiac, skeletal, and smooth muscle genes and is essential for cardiogenesis Black and Olson, 1998;McKinsey et al., 2002). GATA4, a GATA family zinc finger protein which directly binds to the DNA sequence element (A/ T)GATA(A/G), is expressed in the cardiac lineage throughout embryonic development and in adulthood, and is required for early heart formation (Arceci et al., 1993;Kelley et al., 1993;Ip et al., 1994;Kuo et al., 1997;Molkentin et al., 1997). Tbx1, Tbx5, and Tbx20, members of the T-box transcription factors, have also been sh...

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

Cited by 21 publications

References 36 publications

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

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

Myocardin-like protein 2 regulates TGFβ signaling in embryonic stem cells and the developing vasculature

Myocardin Marks the Earliest Cardiac Gene Expression and Plays an Important Role in Heart Development

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