Endogenous bone morphogenetic protein antagonists regulate mammalian neural crest generation and survival

Dev Dyn. 2006 Sep;235(9):2507-20. doi: 10.1002/dvdy.20891.

Abstract

We demonstrate here that Chordin and Noggin function as bone morphogenetic protein (BMP) antagonists in vivo to promote mammalian neural crest development. Using Chrd and Nog single and compound mutants, we find that Noggin has a major role in promoting neural crest formation, in which Chordin is partially redundant. BMP signaling is increased in dorsal tissues lacking Noggin and is further increased when Chordin is also absent. The early neural crest domain is expanded with decreased BMP antagonism in vivo. Noggin and Chordin also regulate subsequent neural crest cell emigration from the neural tube. However, reduced levels of these BMP antagonists ultimately result in perturbation of neural crest cell derived peripheral nervous system and craniofacial skeletal elements. Such defects reflect, at least in part, a function to limit apoptosis in neural crest cells. Noggin and Chordin, therefore, function together to regulate both the generation and survival of neural crest cells in mammalian development.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Apoptosis
  • Bone Morphogenetic Protein 2
  • Bone Morphogenetic Proteins / antagonists & inhibitors*
  • Bone Morphogenetic Proteins / metabolism
  • Carrier Proteins / genetics
  • Carrier Proteins / metabolism
  • Cell Movement
  • Cell Survival
  • Facial Bones / embryology
  • Female
  • Glycoproteins / deficiency
  • Glycoproteins / genetics
  • Glycoproteins / metabolism
  • Intercellular Signaling Peptides and Proteins / deficiency
  • Intercellular Signaling Peptides and Proteins / genetics
  • Intercellular Signaling Peptides and Proteins / metabolism
  • Mice
  • Mice, Inbred ICR
  • Mice, Knockout
  • Neural Crest / cytology
  • Neural Crest / embryology*
  • Neural Crest / metabolism*
  • Pregnancy
  • Signal Transduction
  • Skull / embryology
  • Transforming Growth Factor beta / antagonists & inhibitors
  • Transforming Growth Factor beta / metabolism

Substances

  • Bmp2 protein, mouse
  • Bone Morphogenetic Protein 2
  • Bone Morphogenetic Proteins
  • Carrier Proteins
  • Glycoproteins
  • Intercellular Signaling Peptides and Proteins
  • Transforming Growth Factor beta
  • noggin protein
  • chordin