Ann Thorac Surg 2008;85:2099. doi:10.1016/j.athoracsur.2008.03.022
© 2008 The Society of Thoracic Surgeons
Original Articles: Pediatric Cardiac
Invited Commentary
Richard W. Kim, MD
Surgery, Section of Cardiac Surgery, Yale University School of Medicine, 333 Cedar St, 121 FMB, New Haven, CT 06520-8039
(Email: richard.w.kim{at}yale.edu).
In demonstrating the need for endocardial BMP receptor 1a (BMPR1a) expression in atrioventricular (AV) valve development, Kaneko and colleagues [1] confirm important, previously defined work that identified the importance of BMP signaling in endocardial cushion defects and AV valve formation [2, 3]. Significantly, they not only further identify potential downstream molecular targets of BMPR1a signaling in the embryonic heart, but they also delineate the temporal signaling requirements for AV valve development by knocking down endocardial BMPR1a in a time-dependent fashion.
Despite the current focus on bone morphogenic protein-dependent cell signaling in developmental biology, it is interesting that BMPs, of course, were originally identified as critical mediators of cartilage and bone generation [4]. Who would have guessed that the same family of molecules that leads to bone generation is required for the correct development of the AV canal?
Work, such as that presented here, immediately begs the question of whether developmentally requisite BMP signaling, necessary for appropriate valvular growth and development, is also involved in pathologic mitral calcification or in calcific rheumatic disease. By demonstrating that conditional BMPR1a knockouts after E 10.5 develop morphologically normal AV valves, Kaneko and colleagues [1] further provide important evidence that suggests that receptor expression is not necessary for long-term maintenance of valve tissue. The implication is that BMPR1a inhibition may represent a potential target for future intervention in adults to prevent or reduce valvular calcification.
For molecular level dissection of these embryonic developmental pathways, the devil is in the details, and important contributions are often made from incremental changes in study design. This is just such a case. Performed in Dr Thistlewaite's laboratory in San Diego, these observations not only help to focus our understanding of the developing heart, but also help to open our eyes to related pathologic questions that may be pertinent to all cardiac surgeons, developmental biologists, and others alike.
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References
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- Kaneko K, Li X, Zhang X, Lamberti JJ, Jamieson SW, Thistlethwaite PA. Endothelial expression of bone morphogenetic protein receptor Type 1a is required for atrioventricular valve formation Ann Thorac Surg 2008;85:2090-2099.[Abstract/Free Full Text]
- Ma L, Lu MF, Schwartz RJ, Martin JF. Bmp2 is essential for cardiac cushion epithelial-mesenchymal transition and myocardial patterning Development 2005;132:5601-5611.[Abstract/Free Full Text]
- Song L, Fassler R, Mishina Y, Jiao K, Baldwin HS. Essential functions of Alk3 during AV cushion morphogenesis in mouse embryonic hearts Dev Biol 2007;301:276-286.[Medline]
- Lyons KM, Pelton RW, Hogan BLM. Organogenesis and pattern formation in the mouse: RNA distribution patterns suggest a role for Bone Morphogenetic Protein-2A (BMP-2A) Development 1990;109:833-844.[Abstract/Free Full Text]
Related Article
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Endothelial Expression of Bone Morphogenetic Protein Receptor Type 1a is Required for Atrioventricular Valve Formation
- Kan Kaneko, Xiaodong Li, Xiaoxue Zhang, John J. Lamberti, Stuart W. Jamieson, and Patricia A. Thistlethwaite
Ann. Thorac. Surg. 2008 85: 2090-2098.
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