Our laboratory is interested in using quantitative approaches to understand how cell structural components are orchestrated to regulate morphogenesis and growth control.
1. The molecular and cellular basis of single cell delamination.
Cell delamination is a morphogenesis process essential for organ formation during animal development. We have recently established Drosophila embryonic neuroblasts as a genetically and optically tractable system for studying single-cell delamination. We have demonstrated that delaminating neuroblasts undergo pulsatile constriction of their apical domain as a first step of leaving the epithelial layer. We have shown that a dynamic myosin network of flows and pulses exist in both delaminating neuroblasts and their neighbors, but quantitative differences in medial myosin pulse intensity and frequency are critical to distinguish delaminating neuroblasts from their neighbors. The neuroblast fate is set apart from its neighbors through a classical lateral inhibition process mediated by Notch-Delta signaling activity. While we have demonstrated that the fate-determining Notch activity is critical in organizing the myosin network to drive delamination, an important question remains unaddressed: How is the fate-determining Notch signal activity translated into a highly dynamic and quantitatively refined myosin network that drives neuroblast delamination? We therefore compared transcriptomes in embryos injected with water and Delta dsRNA at the onset of neuroblast delamination and identified a set of differentially expressed genes. We then performed genetic screening from the gene list and identified several novel components regulating neuroblast delamination. These newly identified components will allow us to build the molecular network from cell-cell signaling to the mechanical processes of single cell delamination.
2. Cell structural components in growth control.
The epithelial tissue architecture and proliferation control are intertwining processes. Proteins essential for maintaining epithelial structures have been shown to participate in proliferation control. We have previously shown that the cytoskeletal spectrin network regulates growth through modulating Hippo signaling activity. We are currently studying a group of “neoplastic tumor suppressor genes” (nTSG), which often encode cell structural components and display mutant phenotypes with high similarity to human tumors.