title: Modeling the morphodynamic galectin patterning network of the developing avian limb skeleton.
abstract: We present a mathematical model for the morphogenesis and patterning of the mesenchymal condensations that serve as primordia of the avian limb skeleton. The model is based on the experimentally established dynamics of a multiscale regulatory network consisting of two glycan-binding proteins expressed early in limb development: CG (chicken galectin)-1A, CG-8 and their counterreceptors that determine the formation, size, number and spacing of the "protocondensations" that give rise to the condensations and subsequently the cartilaginous elements that serve as the templates of the bones. The model, a system of partial differential and integro-differential equations containing a flux term to represent local adhesion gradients, is simulated in a "full" and a "reduced" form to confirm that the system has pattern-forming capabilities and to explore the nature of the patterning instability. The full model recapitulates qualitatively and quantitatively the experimental results of network perturbation and leads to new predictions, which are verified by further experimentation. The reduced model is used to demonstrate that the patterning process is inherently morphodynamic, with cell motility being intrinsic to it. Furthermore, subtle relationships between cell movement and the positive and negative interactions between the morphogens produce regular patterns without the requirement for activators and inhibitors with widely separated diffusion coefficients. The described mechanism thus represents an extension of the category of activator-inhibitor processes capable of generating biological patterns with repetitive elements beyond the morphostatic mechanisms of the Turing/Gierer-Meinhardt type.
authors.affiliation: Department of Mathematics, Western Washington University, Bellingham, WA 98229, USA. Electronic address: glimmt@wwu.edu.
authors.forename: T
authors.initials: T
authors.lastname: Glimm
authors.affiliation: Life Sciences Division, Lawrence Berkeley National Laboratory, Berkeley, CA 94720, USA. Electronic address: RBhat@lbl.gov.
authors.forename: R
authors.initials: R
authors.lastname: Bhat
authors.affiliation: Department of Cell Biology & Anatomy, Basic Sciences Building, Valhalla, NY 10595, USA. Electronic address: newman@nymc.edu.
authors.forename: S A
authors.initials: SA
authors.lastname: Newman
mesh_terms: D000818:Animals; D019521:Body Patterning; D001842:Bone and Bones / Q000196:embryology*; D002448:Cell Adhesion; D002452:Cell Count; D002645:Chickens; D020219:Chondrogenesis; D003198:Computer Simulation; D005121:Extremities / Q000196:embryology*; D037161:Galectins / Q000378:metabolism*; D008954:Models, Biological; D009716:Numerical Analysis, Computer-Assisted; D015203:Reproducibility of Results; D013997:Time Factors
chemical_list: D037161:Galectins
keywords: Chondrogenesis; Limb development; Nonlocal reaction–diffusion model; Partial integro-differential equations; Pattern formation