Instytut Podstawowych Problemów Techniki
Polskiej Akademii Nauk


Ramray Bhat

Ostatnie publikacje
1.  Glimm T., Kaźmierczak B.A., Newman S.A., Bhat R., A two-galectin network establishes mesenchymal condensation phenotype in limb development, MATHEMATICAL BIOSCIENCES, ISSN: 0025-5564, DOI: 10.1016/j.mbs.2023.109054, Vol.365, pp.1-11, 2023

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.

Słowa kluczowe:
Limb development,Galectins,Cell state transition,Switch-like regulatory network,Ordinary differential equations,Lyapunov function,Saddle–node bifurcation

Afiliacje autorów:
Glimm T. - Western Washington University (US)
Kaźmierczak B.A. - IPPT PAN
Newman S.A. - New York Medical College (US)
Bhat R. - inna afiliacja

Kategoria A Plus


logo ippt            ul. Pawińskiego 5B, 02-106 Warszawa
  +48 22 826 12 81 (centrala)
  +48 22 826 98 15

Znajdź nas

© Instytut Podstawowych Problemów Techniki Polskiej Akademii Nauk 2024