"Cytoskeletal Regulation from Molecules to Morphogenesis"

Actin regulators are essential for the cell shape changes and protrusive behaviors required for cell motility, morphogenesis, and cancer metastasis. While many key actin regulators have been identified and individually characterized in vitro and single cell contexts, critical questions remain about how they work in parallel and together to generate the diverse array of actin structures seen in vivo during normal development. Among the most critical actin-based structures driving development and homeostasis are the dynamic combinations of lamellipodia and filopodia characterizing different cell types. We use Diaphanous-class formins (Dia) and Enabled/VASP (Ena) proteins as models to address these fundamental questions. Both associate with actin filament barbed ends and promote actin polymerization. We have taken an interdisciplinary approach to attack this problem at a number of different scales, combining single molecule imaging, computational analysis of cell protrusive behavior in cell culture, and analysis of cell migration during normal embryonic development. These studies reveal how the different biochemical properties of Enabled and Diaphanous allow them to drive distinctive protrusive behaviors, reveal how their physical interaction with one another modifies this, and reveal how different cells in vivo use different combinations of regulators to drive their unique suites of cell protrusions.