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      BMP type II receptor regulates positioning of outflow tract and remodeling of atrioventricular cushion during cardiogenesis

      , , , , ,
      Developmental Biology
      Elsevier BV

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          Abstract

          Signaling of bone morphogenetic protein (BMP) via type I and type II receptors is involved in multiple processes contributing to cardiogenesis. To investigate the role of the BMP type II receptor (BMPRII) in heart development, the BMPRII gene was deleted throughout the embryo during gastrulation using a Mox2-Cre transgene. BMPRII(flox/-);Mox2-Cre mice exhibited cardiac defects including double-outlet right ventricle, ventricular septal defect (VSD), atrioventricular (AV) cushion defects, and thickened valve leaflets. To characterize the tissue-specific functions of BMPRII in cardiogenesis, a series of Cre transgenes (alphaMHC-, Tie2-, Wnt1-, and SM22alpha-Cre) was employed. Interestingly, myocardial development was normal when the BMPRII gene was deleted in myocardial cells using Mox2-Cre, alphaMHC-Cre, or SM22alpha-Cre transgenes, suggesting that signaling by other BMP type II receptors may compensate for the absence of BMPRII in the myocardial cells. AV cushion defects including atrial septal defect, membranous VSD, and thickened valve leaflets were found in BMPRII(flox/-);Tie2-Cre mice. Abnormal positioning of the aorta was observed in BMPRII(flox/-);Wnt1-Cre and BMPRII(flox/-);SM22alpha-Cre mice. Taken together, these results demonstrate that endocardial BMPRII expression is required for septal formation and valvulogenesis. Moreover, mesenchymal BMPRII expression in the outflow tract cushion is required for proper positioning of the aorta.

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          Author and article information

          Journal
          Developmental Biology
          Developmental Biology
          Elsevier BV
          00121606
          July 2009
          July 2009
          : 331
          : 2
          : 167-175
          Article
          10.1016/j.ydbio.2009.04.032
          2745439
          19409885
          6a0d8836-f8e0-4021-b6d1-495ba91e74de
          © 2009

          https://www.elsevier.com/tdm/userlicense/1.0/

          https://www.elsevier.com/open-access/userlicense/1.0/

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