A two-galectin network establishes mesenchymal condensation phenotype in limb development

Glimm, T and Kaźmierczak, B and Newman, SA and Bhat, R (2023) A two-galectin network establishes mesenchymal condensation phenotype in limb development. In: Elsevier Inc., 365 .

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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. © 2023

Item Type:	Journal Article
Publication:	Elsevier Inc.
Publisher:	Elsevier Inc.
Additional Information:	The copyright for this article belongs to the Elsevier Inc.
Keywords:	Adhesion; Adhesives; Bifurcation (mathematics); Cell culture; Cell proliferation; Ordinary differential equations, Cell state; Cell state transition; Embryonics; Galectins; Limb development; Lyapunov's functions; Regulatory network; Saddle node bifurcation; State transitions; Switch-like regulatory network, Lyapunov functions, galectin; galectin 1; galectin 8, adhesion; bifurcation; cell; limb; phenotype; protein, Article; cell adhesion; cell culture; cell density; cell interaction; cell population; cell surface; cellular, subcellular and molecular biological phenomena and functions; chick; chondrogenesis; controlled study; degradation; diffusion; in vitro study; limb development; mesenchymal condensation; mesenchyme cell; nonhuman; phenotype; prediction; protein expression; protein function; protein polymerization
Department/Centre:	Division of Biological Sciences > Molecular Reproduction, Development & Genetics Division of Interdisciplinary Sciences > Centre for Biosystems Science and Engineering
Date Deposited:	28 Nov 2023 07:00
Last Modified:	28 Nov 2023 07:00
URI:	https://eprints.iisc.ac.in/id/eprint/83386

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