The main goal of our lab is to understand the molecular mechanisms of neural development and neurodegeneration. We mainly utilize nematode C. elegans as our model organism, which has been proved as a very powerful system to understand the conserved molecular mechanisms of neural development, such as axon guidance and synapse formation. Formation of neural circuit requires precise regulation of both axonal and dendritic guidance. Many axon guidance molecules have been identified and characterized in the last several decades. However, little is known how dendrites are guided during development. During Wei’s postdoctoral training with Dr. David Sherwood at Duke University and Dr. Kang Shen at Stanford University, he has identified several novel dendritic guidance molecules. Among these, LECT-2, the homologue of human LECT2, acts as a co-ligand with two cell adhesion molecules SAX-7/L1CAM and MNR-1/Menorin. These three molecules form a co-ligand complex, which is recognized by the dendritic receptor DMA-1. Activation of DMA-1 requires the presence of each molecule, suggestive of a co-incidence detection mode of recognition to specify the precise location of dendritic arbors. He also found HPO-30, a claudin-like protein, functions as a co-receptor of DMA-1. HPO-30 and DMA-1 recruit WAVE regulatory complex and TIAM-1/RacGEF, respectively, to promote actin assembly and dendrite formation. To the best of our knowledge, this is the first case to show that a claudin acts as a signaling molecule rather than as a component of tight junctions during neural development.

The main research topics in the Zou lab are:

(1)   Molecular mechanisms of dendrite guidance.

(2)   Molecular mechanisms of axonal and dendritic degeneration.

(3)   Identification of small molecules which can suppress neurodegeneration.

We hope that our research will help to develop effective treatments for neurodegeneration diseases such as Alzheimer’s disease and Parkinson’s disease.