Mechanical and Electrical Guidance of Collective Cell Migration in vivo

ongoing

Directional collective cell migration (dCCM) is key for cellular clusters to reach their target tissues in embryogenesis, tissue repair, and metastasis. Though cells interact with chemical and physical cues when migrating in vivo, the field has mostly focused on studying the chemical guidance (chemotaxis) of dCCM- and the role of physical cues is underappreciated. As chemotaxis is not sufficient to explain dCCM in native contexts, the mechanisms that guide dCCM in vivo remain unclear. Thus, our overall goal is to challenge the classic chemocentric view by addressing whether and how biophysical cues such as mechanical and electrical signals contribute to dCCM in vivo. To tackle this challenging aim, we will study durotaxis (mechanical guidance) and electrotaxis (electrical guidance) at two levels: i) Tissue level, to map mechanical and electrical properties in vivo and test their relative contribution to dCCM and ii) Cellular level, to explore the mechanisms by which cells respond and integrate these biophysical cues. To address this, we will take advantage of the innovative toolbox we developed to study mechanical and electrical cues in vivo. As dCCM occurs in different biological contexts, we propose to generalise our results by studying dCCM of Xenopus neural crest (NCs) in embryogenesis (WP1, WP2), and the migration of the recently discovered Regeneration Organizing Cells (ROCs) in Xenopus tail regeneration (WP3). Demonstrating durotaxis and electrotaxis in vivo has proven to be a challenging goal. Thus, we expect our research to be a breakthrough across fields, bringing new perspectives and tools to study the biophysics of dCCM in vivo for the first time. Finally, this proposal will open new research avenues for my lab and for the field, in which the interplay of biophysical and biochemical cues from the environment could be studied, paving the way to the formulation of a novel and more integrative view of dCCM, and other cell and developmental processes.