The Hedgehog (Hh) signalling pathway plays a crucial role in animal embryonic and organ development. In the wing imaginal disc of Drosophila melanogaster, Hh is induced and diffuses from the posterior compartment to activate the corresponding pathway in cells immediately anterior to the boundary. In these boundary cells, the Hh gradient induces target genes in distinct domains as a function of the Hh concentration. One Hh target is its own receptor Patched (Ptc), which sequesters Hh and impedes further diffusion, thereby refining the boundary.
We have delineated a multivalued logical model of the patterning process defining the cellular anterior-posterior boundary that includes the formation of Hh gradient and Hh signalling transduction. This model accounts for the activation of Hh target genes mediated by positive (CiA) and negative (CiR) regulatory products of the gene cubitus interruptus (ci). Wild-type and mutant simulations are carried out to assess the coherence of the model with experimental data and to obtain biological insights into this fundamental process.
In addition to recapitulating experimental data, our logical analysis leads to the delineation of three crucial features. First, CiA should be present in all boundary cells. Second, Ptc is regulated by CiA, but also tentatively by CiR. Third, the model predicts that Engrailed acts at different functional levels in boundary and posterior cells.