Dynamical mechanisms for skeletal pattern formation in the vertebrate limb

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-βs). 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 FGFdependent 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-β and inhibitor concentrations in the developing limb bud.

Shared rules of development predict patterns of evolution in vertebrate segmentation

“…Our results contribute to increasing evidence that activator-inhibitor interactions are involved in limb, digit and somite segmentation, and could reflect a universal design principle 4,[30][31][32][33][34][35] , but while confirmatory these results do not clarify the identity of the molecule(s) or the exact developmental mechanisms involved. We argue that the value of using the IC model is that, while previous models describe how segments form, they make no predictions about how they vary in size, and imply that elements are either independently formed or that segment proportions are largely the result of selection on later developmental events such as growth.…”

Evolutionary Developmental Biology and the Limits of Philosophical Accounts of Mechanistic Explanation

“…In addition to a plethora of fossil studies and experimental investigations in extant species (e.g., chicken), the formation of the broadest aspects of the shape of different skeletal elements and their basic spatial position has been mathematically modeled using activator-inhibitor systems (Hentschel et al 2004;Newman et al 2008;Newman and Müller 2005). This basic skeletal pattern in the adult organism is a fairly qualitative phenomenon and its developmental explanation involves quantitative models.…”

Bone Formation: Biological Aspects and Modelling Problems

“…It is natural to wonder whether a similar result could be obtained for the condensation process under consideration here. Checking this point might require a detailed analysis of mathematical models as those recently derived by Hentschel et al [44] to describe precartilage condensation.…”