MODELING THE EFFECT OF CALPAIN ON DORSAL-VENTRAL AXIS PATTERNING IN DROSOPHILA MELANOGASTER

Early development of Drosophila melanogaster embryo is marked by the establishment of molecular patterns that guide the formation of morphological axis, determinants for the whole process of building an organism. One of those patterns is the nuclear Dorsal protein gradient, main regulator of dorsal-ventral axis formation. Modeling a biochemical reaction network involving key proteins of Toll pathway in D.melanogaster is enough to explain some of the main features of gradient formation. However, recent studies have demonstrated that a protease called Calpain A has an important role to fine-tune the gradient magnitude. Calpain A promotes the cleavage of Cactus, a protein that binds Dorsal and inhibits its nuclear entry. The goal of the present study is to model a chemical reaction network adding Calpain A and propose a new mechanism to explain the effect of Calpain on Dorsal gradient inside the developing egg. We model chemical reaction networks through differential equations using mass-action kinetics and test different hypothesis for mechanisms by building different networks. Through a Bayesian approach, we inferred kinetic parameters using a Monte Carlo algorithm called Hamiltonian Monte Carlo and data available in the literature. Our results show that cleavage by Calpain A could be interpreted as an step of the Toll independent Cactus degradation pathway.