Disease relevance of Mkl2

• We show that mice homozygous for an MRTF-B loss-of-function mutation die during mid-gestation from a spectrum of cardiovascular defects that includes abnormal patterning of the branchial arch arteries, double-outlet right ventricle, ventricular septal defects, and thin-walled myocardium [1].
• MRTF-B homozygous mutants die in late gestation with vascular defects and liver hemorrhage [2].

High impact information on Mkl2

• The phenotype of MRTF-B mutant mice is distinct from that of mice lacking myocardin, revealing unique roles for these serum response factor coactivators in the development of different subsets of smooth muscle cells in vivo [1].
• Requirement of myocardin-related transcription factor-B for remodeling of branchial arch arteries and smooth muscle differentiation [1].
• Myocardin-related transcription factor B is required in cardiac neural crest for smooth muscle differentiation and cardiovascular development [3].
• MRTF-B is expressed in the premigratory neural crest, in rhombomeres 3 and 5, and in the neural crest-derived mesenchyme surrounding the aortic arch arteries [3].
• Remarkably, the observed pathology was rescued and viable mice generated by intercrossing MRTF-B mutants with mice expressing Cre recombinase under the transcriptional control of the neural crest-restricted Wnt-1 promoter, which results in restoration of normal MRTF-B expression in the neural crest [3].

Biological context of Mkl2

• Taken together, these studies reveal that MRTF-B plays a critical role in regulating differentiation of cardiac neural crest cells into smooth muscle and demonstrate that neural crest-derived smooth muscle differentiation is specifically required for normal cardiovascular morphogenesis [3].
• Myocardin-related transcription factor B is required for normal mouse vascular development and smooth muscle gene expression [2].

Other interactions of Mkl2

• These data support our hypothesis that MRTF-B has a unique role in regulating smooth muscle genes important for liver, yolk sac, and portal vascular development [2].

References