As a new focus in my lab, we investigate how mechanical signals modulate the genetic and biochemical network behaviors. The segmentation clock slows down while cell motility increases and tissue stiffness decreases from posterior to anterior. A recent study in mouse embryos suggested that the oscillatory transition of single PSM cells may be controlled by expression of YAP, a stiffness sensor that regulates the mechanotransduction. We will study how surface rigidity, by triggering ROCK signaling and F-actin polymerization and activating YAP, may play a key role in the spatiotemporal pattern of the segmentation clock. The process is further complicated by signaling gradients of Fgf and Wnt that promote cell motility and proliferation in posterior and RA that promotes cell differentiation in anterior. To quantitatively manipulate biochemical and mechanical signals, we have developed microfluidic methods to successfully grow dissected PSM tissues or dissociated single PSM cells in vitro for a long-term (more than 24 hours) where the PSM tissue can elongate and differentiate into multiple somites. We will apply an optogenetic tool to manipulate the Fgf/Wnt signal with spatiotemporal accuracy. Collaborating with Jianping Fu at UM, we will use the patterned microcontact printing technique to culture single PSM cells on PDMS micropost arrays that quantitively define surface rigidity. We will integrate mathematical modeling with techniques of nanoscale mechanical regulation and optogenetics to understand the mechanobiology of embryonic morphogenesis.