BMP receptor IA is required in mammalian neural crest cells for development of the cardiac outflow tract and ventricular myocardium

Development. 2004 May;131(9):2205-18. doi: 10.1242/dev.01086. Epub 2004 Apr 8.

Abstract

The neural crest is a multipotent, migratory cell population arising from the border of the neural and surface ectoderm. In mouse, the initial migratory neural crest cells occur at the five-somite stage. Bone morphogenetic proteins (BMPs), particularly BMP2 and BMP4, have been implicated as regulators of neural crest cell induction, maintenance, migration, differentiation and survival. Mouse has three known BMP2/4 type I receptors, of which Bmpr1a is expressed in the neural tube sufficiently early to be involved in neural crest development from the outset; however, earlier roles in other domains obscure its requirement in the neural crest. We have ablated Bmpr1a specifically in the neural crest, beginning at the five-somite stage. We find that most aspects of neural crest development occur normally; suggesting that BMPRIA is unnecessary for many aspects of early neural crest biology. However, mutant embryos display a shortened cardiac outflow tract with defective septation, a process known to require neural crest cells and to be essential for perinatal viability. Surprisingly, these embryos die in mid-gestation from acute heart failure, with reduced proliferation of ventricular myocardium. The myocardial defect may involve reduced BMP signaling in a novel, minor population of neural crest derivatives in the epicardium, a known source of ventricular myocardial proliferation signals. These results demonstrate that BMP2/4 signaling in mammalian neural crest derivatives is essential for outflow tract development and may regulate a crucial proliferation signal for the ventricular myocardium.

Publication types

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

MeSH terms

  • Animals
  • Bone Morphogenetic Protein 2
  • Bone Morphogenetic Protein 4
  • Bone Morphogenetic Protein Receptors, Type I
  • Bone Morphogenetic Proteins / metabolism
  • Cardiovascular System / anatomy & histology
  • Cell Differentiation
  • Embryo, Mammalian / anatomy & histology
  • Embryo, Mammalian / physiology*
  • Gene Expression Regulation, Developmental
  • Gestational Age
  • Heart Defects, Congenital
  • Heart Ventricles / anatomy & histology
  • Heart Ventricles / growth & development*
  • Mice
  • Mice, Knockout
  • Morphogenesis / physiology*
  • Myocardium / cytology
  • Myocardium / metabolism*
  • Neural Crest / cytology*
  • Neural Crest / metabolism
  • Pericardium / cytology
  • Pericardium / metabolism
  • Protein Serine-Threonine Kinases / genetics
  • Protein Serine-Threonine Kinases / metabolism*
  • Proto-Oncogene Proteins / metabolism
  • Receptors, Growth Factor / genetics
  • Receptors, Growth Factor / metabolism*
  • Signal Transduction / physiology
  • Somites / cytology
  • Somites / metabolism
  • Transforming Growth Factor beta*
  • Wnt Proteins
  • Zebrafish Proteins*

Substances

  • Bmp2 protein, mouse
  • Bmp4 protein, mouse
  • Bone Morphogenetic Protein 2
  • Bone Morphogenetic Protein 4
  • Bone Morphogenetic Proteins
  • Proto-Oncogene Proteins
  • Receptors, Growth Factor
  • Transforming Growth Factor beta
  • Wnt Proteins
  • Zebrafish Proteins
  • bmp4 protein, zebrafish
  • Protein Serine-Threonine Kinases
  • Bmpr1a protein, mouse
  • Bone Morphogenetic Protein Receptors, Type I