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

William C Hamilton, Magdalena A Stolarska, Afshan Ismat

Developmental dynamics : an official publication of the American Association of Anatomists 2022 Jul

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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. 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. 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. © 2022 American Association for Anatomy.

Citation

William C Hamilton, Magdalena A Stolarska, Afshan Ismat. Simulation and in vivo experimentation predict AdamTS-A location of function during caudal visceral mesoderm migration in Drosophila. Developmental dynamics : an official publication of the American Association of Anatomists. 2022 Jul;251(7):1123-1137