BMPs Regulate the Oft Development via miRNAs
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Congenital heart diseases (CHD) are the leading cause of infant mortality and morbidity. Defects of the outflow tract (OFT) make up a large percentage of human CHD. In my study, I focused on the role of Bone morphogenetic protein (BMP) on heart development. I investigated Bmp signaling in OFT development using conditional knocking out Bmps, including Bmp2, -4 and -7. Deletion of Bmp4/7 in second heart field (SHF) results in persistent truncus arteriosus (PTA), which is caused by endothelial to mesenchyme transition (EMT) defect. I found that Vegfa (vascular endothelial growth factor a) is a downstream target of Bmp and miR-17-92. Repression of Vegfa in OFT is important for the proper onset of EMT at E10.5. Further exploration on Bmp2/4/7 mutation indicates that loss of Bmp signal disrupt the smooth muscle differentiation and maintenance. Similar with observations on Marfan syndrome mouse model, Bmp2/4/7 triple CKO embryos exhibited significant upregulation of Tgf-β signal activity. Alternation of SMC feature is likely due to the persistence of Isl-1 expression. Haploinsufficiency of Bmp4 triggered early onset of aorta aneurysm in Fbn-1^(C1039G/+) mice. These data indicate that Bmps not only play an important role in embryonic cardiogenesis, but also are critical for the cell fate differentiation and maintenance in adulthood.
Bai, Yan (2014). BMPs Regulate the Oft Development via miRNAs. Doctoral dissertation, Texas A & M University. Available electronically from