Simulation and in vivo experimentation predict AdamTS-A location of function during caudal visceral mesoderm migration in Drosophila

Abstract

Background: Caudal visceral mesoderm (CVM) cells migrate as a loose collective along the trunk visceral mesoderm (TVM) and are surrounded by extracellular matrix (ECM). In this study, we examined how one extracellular protease, AdamTS-A, facilitates CVM migration. Results: A comparison of mathematical simulation to experimental results suggests that location of AdamTS-A action in CVM cells is on the sides of the cell not in contact with the TVM, predominantly at the CVM-ECM interface. CVM migration from a top-down view showed CVM cells migrating along the outside of the TVM substrate in the absence of AdamTS-A. Moreover, overexpression of AdamTS-A resulted in similar, but milder, mis-migration of the CVM. These results contrast with the salivary gland where AdamTS-A is proposed to cleave connections at the trailing edge of migrating cells. Subcellular localization of GFP-tagged AdamTS-A suggests that this protease is not limited to functioning at the trailing edge of CVM cells. Conclusion: Using both in vivo experimentation and mathematical simulations, we demonstrated that AdamTS-A cleaves connections between CVM cells and the ECM on all sides not attached to the TVM. Clearly, AdamTS-A has a more expansive role around the entire cell in cleaving cell-ECM attachments in cells migrating as a loose collective.