Dynamical mechanisms for skeletal pattern formation in the vertebrate limb

Proc Biol Sci. 2004 Aug 22;271(1549):1713-22. doi: 10.1098/rspb.2004.2772.

Abstract

We describe a 'reactor-diffusion' mechanism for precartilage condensation based on recent experiments on chondrogenesis in the early vertebrate limb and additional hypotheses. Cellular differentiation of mesenchymal cells into subtypes with different fibroblast growth factor (FGF) receptors occurs in the presence of spatio-temporal variations of FGFs and transforming growth factor-betas (TGF-betas). One class of differentiated cells produces elevated quantities of the extracellular matrix protein fibronectin, which initiates adhesion-mediated preskeletal mesenchymal condensation. The same class of cells also produces an FGF-dependent laterally acting inhibitor that keeps condensations from expanding beyond a critical size. We show that this 'reactor-diffusion' mechanism leads naturally to patterning consistent with skeletal form, and describe simulations of spatio-temporal distribution of these differentiated cell types and the TGF-beta and inhibitor concentrations in the developing limb bud.

Publication types

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

MeSH terms

  • Animals
  • Body Patterning / physiology*
  • Cartilage / cytology
  • Cartilage / embryology
  • Cell Adhesion / physiology
  • Cell Differentiation / physiology
  • Chondrogenesis / physiology*
  • Extremities / embryology*
  • Fibroblast Growth Factors / metabolism
  • Fibronectins / metabolism
  • Mesoderm / physiology
  • Models, Biological*
  • Receptors, Fibroblast Growth Factor / metabolism
  • Transforming Growth Factor beta / metabolism
  • Vertebrates / embryology*

Substances

  • Fibronectins
  • Receptors, Fibroblast Growth Factor
  • Transforming Growth Factor beta
  • Fibroblast Growth Factors