Lu, Xiaowei

Xiaowei  Lu

Xiaowei Lu

Primary Appointment

Associate Professor, Cell Biology


  • BS, Biochemistry, Beijing University
  • PhD, Biology, Massachusetts Institute of Technology
  • Postdoc, Developmental Neurobiology, University of California, San Francisco

Contact Information


Research Interests

Developmental regulation of planar cell polarity in the mammalian nervous system

Research Description

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.

It has been shown that an evolutionarily conserved noncanonical,

b-catenin-independent Wnt pathway regulates PCP and is involved in diverse

processes such as neural tube closure and cochlear hair cell morphogenesis.

Recently, in a gene trap screen in the mouse, we identified PTK7, an

atypical receptor tyrosine kinase, as a novel regulator of PCP in

vertebrates. Interestingly, homologs of several vertebrate PCP genes,

including PTK7, have not been implicated in PCP signaling in Drosophila,

suggesting that vertebrates have evolved novel strategies to regulate PCP.

Using PTK7 as an entry point, we are taking a combination of biochemical,

genetic and cell biological approaches to further elucidate signaling

mechanisms by which the PCP pathway exert its effect on cellular machinery,

such as the cytoskeleton and protein trafficking network.

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.

Selected Publications