Role of Bone Morphogenetic Proteins in Valvulogenesis

  • Russell A. Gould
  • Jonathan T. ButcherEmail author


Valvulogenesis is a complex process involving the formation and morphogenesis of the atrioventricular and semilunar valves. The early embryonic heart is a single myocardial tube lined with endocardial cells. During the looping process, simultaneous valve formation initiates by deposition of hyaluronan-rich gelatinous matrix, called cardiac jelly, forming swellings, which project into the lumen. At the onset of Hamburger and Hamilton (HH14-, E9.0 in mouse), a process called EMT (epithelial-mesenchymal transition) takes place in which the lining of endocardial cell swellings differentiated from an EMT phenotype. This process is associated with downregulation of cell-cell contacts, such as E-cadherin and PECAM1, the acquisition of cell-matrix adhesions, and cytoskeleton rearrangement [1]. The invasiveness of the mesenchymal phenotype is critical, as these cells dive into the hyaluronan-rich cardiac jelly, degrade the underlying matrix, and deposit newly synthesized collagen I, II, III, versican, and other proteoglycans [2]. These newly populated mesenchymal swellings, called “cushions”, form in pairs that oppose each other during the cardiac cycle to act as primitive valves by maintaining unidirectional blood flow [3]. One pair of cushions develops in the atrioventricular (AV) canal, and two (proximal and distal) develop in the outflow tract (OFT). Underlying this valve formation process, bone-morphogenetic proteins (BMP) have been established as critical cytokines. Using both in-vitro and in-vivo models, dysfunction of this pathway has been associated with a number of congenital valve defects, and their role will now be discussed.


Bone Morphogenetic Protein Bone Morphogenetic Protein Signaling Endocardial Cushion Bone Morphogenetic Protein Receptor Semilunar Valve 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


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Copyright information

© Springer-Verlag London 2013

Authors and Affiliations

  1. 1.Department of Biomedical EngineeringCornell UniversityIthacaUSA
  2. 2.Department of Biomedical EngineeringCornell UniversityIthacaUSA

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