A Two-Galectin Network Establishes Mesenchymal Condensation Phenotype in Limb Development

Authors

T Glimm, Department of Mathematics, Western Washington University, Bellingham, WA, 98229, USA.
B Kaźmierczak, Institute of Fundamental Technological Research Polish Academy of Sciences, 02-106, Warsaw, Poland.
S A. Newman, Department of Cell Biology and Anatomy, New York Medical College, Valhalla, New York, NY, 10595, USA.
R Bhat, Department of Developmental Biology and Genetics, Indian Institute of Science, Bangalore 560012, India; Department of Bioengineering, Indian Institute of Science, Bangalore 560012, India. Electronic address: ramray@iisc.ac.in.

Author Type(s)

Faculty

DOI

10.1016/j.mbs.2023.109054

Journal Title

Mathematical Biosciences

First Page

109054

Document Type

Article

Publication Date

11-1-2023

Department

Rehabilitation Sciences

Abstract

Previous work showed that Gal-1A and Gal-8, two proteins belonging to the galactoside-binding galectin family, are the earliest determinants of the patterning of the skeletal elements of embryonic chicken limbs, and further, that their experimentally determined interactions in the embryonic limb bud can be interpreted via a reaction-diffusion-adhesion (2GL: two galectin plus ligands) model. Here, we use an ordinary differential equation-based approach to analyze the intrinsic switching modality of the 2GL network and characterize the network behavior independent of the diffusive and adhesive arms of the patterning mechanism. We identify two states: where the concentrations of both the galectins are respectively, negligible, and very high. This bistable switch-like system arises via a saddle-node bifurcation from a monostable state. For the case of mass-action production terms, we provide an explicit Lyapunov function for the system, which shows that it has no periodic solutions. Our model therefore predicts that the galectin network may exist in low expression and high expression states separated in space or time, without any intermediate states. We test these predictions in experiments performed with high density cultures of chick limb mesenchymal cells and observe that cells inside precartilage protocondensations express Gal-1A at a much higher rate than those outside, for which it was negligible. The Gal-1A and -8-based patterning network is therefore sufficient to partition the mesenchymal cell population into two discrete cell states with different developmental (chondrogenic vs. non-chondrogenic) fates. When incorporated into an adhesion and diffusion-enabled framework this system can generate a spatially patterned limb skeleton.

Recommended Citation

Glimm, T., Kaźmierczak, B., Newman, S. A., & Bhat, R. (2023). A Two-Galectin Network Establishes Mesenchymal Condensation Phenotype in Limb Development. Mathematical Biosciences, 365, 109054. https://doi.org/10.1016/j.mbs.2023.109054