Endocardial cushion and myocardial defects after cardiac myocyte-specific conditional deletion of the bone morphogenetic protein receptor ALK3

Proc Natl Acad Sci U S A. 2002 Mar 5;99(5):2878-83. doi: 10.1073/pnas.042390499. Epub 2002 Feb 19.

Abstract

Receptors for bone morphogenetic proteins (BMPs), members of the transforming growth factor-beta (TGFbeta) superfamily, are persistently expressed during cardiac development, yet mice lacking type II or type IA BMP receptors die at gastrulation and cannot be used to assess potential later roles in creation of the heart. Here, we used a Cre/lox system for cardiac myocyte-specific deletion of the type IA BMP receptor, ALK3. ALK3 was specifically required at mid-gestation for normal development of the trabeculae, compact myocardium, interventricular septum, and endocardial cushion. Cardiac muscle lacking ALK3 was specifically deficient in expressing TGFbeta2, an established paracrine mediator of cushion morphogenesis. Hence, ALK3 is essential, beyond just the egg cylinder stage, for myocyte-dependent functions and signals in cardiac organogenesis.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Bone Morphogenetic Protein Receptors, Type I
  • Bone Morphogenetic Proteins / metabolism
  • Cell Line
  • Female
  • Gene Expression
  • Heart / embryology*
  • Male
  • Mice
  • Morphogenesis
  • Mutagenesis
  • Myocardium / pathology*
  • Protein-Serine-Threonine Kinases*
  • Receptors, Growth Factor*
  • Receptors, Transforming Growth Factor beta / genetics
  • Receptors, Transforming Growth Factor beta / physiology*
  • Transforming Growth Factor beta / genetics
  • Transforming Growth Factor beta2

Substances

  • Bone Morphogenetic Proteins
  • Receptors, Growth Factor
  • Receptors, Transforming Growth Factor beta
  • Transforming Growth Factor beta
  • Transforming Growth Factor beta2
  • Protein-Serine-Threonine Kinases
  • Bmpr1a protein, mouse
  • Bone Morphogenetic Protein Receptors, Type I