Associate Professor, Cell Biology
- BS, Biochemistry, Beijing University
- PhD, Biology, Massachusetts Institute of Technology
- Postdoc, Developmental Neurobiology, University of California, San Francisco
Developmental regulation of planar cell polarity in the mammalian nervous system
Cell polarity is tightly coupled to specialized cell functions and is fundamental to many cellular processes in development and disease. Two forms of epithelial polarity have been observed: one along the apical-basal axis, and one orthogonal to the apical-basal axis known as planar cell polarity (PCP). The Lu lab is interested in dissecting the signaling events that generate planar asymmetry and the resulting cellular behaviors during mammalian development, with a specific focus on two types of polarized cells in the nervous system, namely neuroepithelial cells and neurons.
The cochlear sensory epithelium of the mouse offers an attractive system to study PCP at a single cell resolution both in vivo and in organotypic cultures. PCP is manifested by the asymmetric orientation of the hair cell stereocilia, an actin-rich structure responsible of mechanotransduction. Using a variety of genetic and molecular manipulations and imaging techniques, experiments are underway to better understand the sequence of events that lead to coordinated polarized outgrowth of stereocilia across the sensory epithelium.
We are extending our analysis of the PCP pathway into the development of the central nervous system. Our preliminary analysis of mutant phenotype suggests that PCP pathway is involved in patterning certain regions of the CNS. Currently we are investigating the molecular pathway that underlies the patterning defect. Furthermore, aided by expression studies, we hypothesize that PCP signaling also functions in later aspects of CNS development, such as cell and axon migration and target selection. We plan to use transgenic mice and in vitro neuronal cultures to test this hypothesis.
Ultimately, we hope that our studies will shed light on how the versatile PCP pathway controls cell polarity in different contexts during normal development and how mutations disrupt polarity in related human disease and birth defects.