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

Published

Journal Article

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.

Full Text

Duke Authors

Cited Authors

  • Stottmann, RW; Choi, M; Mishina, Y; Meyers, EN; Klingensmith, J

Published Date

  • May 2004

Published In

Volume / Issue

  • 131 / 9

Start / End Page

  • 2205 - 2218

PubMed ID

  • 15073157

Pubmed Central ID

  • 15073157

International Standard Serial Number (ISSN)

  • 0950-1991

Digital Object Identifier (DOI)

  • 10.1242/dev.01086

Language

  • eng

Conference Location

  • England