The molecular basis for cellular contractility
Contract
Cellular contractility via the Rho pathway plays essential roles throughout the life of single- and multi-cellular organisms. Rho-mediated contraction is essential during cytokinesis to split a dividing cell into two daughters. Rho is also important during cell migration to form adhesions with the substrate and retract the cell’s trailing edge. Contractile events are also required to produce the forces that shape embryonic tissues during early development and for tissue remodeling during wound healing. Misregulation of the Rho pathway, however, has more insidious effects and can lead to pathologies such as hypertension, tissue inflammation, oncogenic transformation, and tumor cell metastasis and angiogenesis. Pharmaceutical intervention in Rho pathway signaling has been used to successfully treat hypertension, cardiovascular disorders, and to promote neuronal regeneration. However, in order to extend the range of treatment options that can target this pathway, we must first identify all of the molecules involved and understand how they interact as a system.

Pathway2
We are using the Drosophila gastrulation pathway as a model system to study how cells perceive signals from the external environment and convert them into changes in cell shape. In flies, this pathway is activated by the secreted protein Folded gastrulation (Fog). Fog is a Drosophila morphogen that drives epithelial sheet remodeling during multiple stages of embryogenesis. It's secreted by epithelial tissues and acts as an autocrine signal to trigger cellular contraction by activating the Rho pathway. Extracellular Fog binds to an unknown receptor that activates the fly G alpha12/13 subunit to stimulate RhoGEF2. RhoGEF2 activates Rho which, in turn, stimulates myosin II via Rho-kinase. In collaboration with Rich Superfine's lab here at UNC, we are using state-of-the-art microfabricated devices to measure forces produced by actin-myosin contraction in Drosophila cells downstream of this signaling circuit.