Dendritic arbors adopt diverse, branched morphologies of varying complexity that are characteristic for a given neuron type. The organization of the dendritic arbors is fundamental to the connectivity and function of a neuron. Although critical to the shape and connectivity of the nervous system, the mechanisms that regulate dendrite morphology are not well understood. In particular, our understandings of membrane molecules that promote and guide patterned dendritic branches are lacking. The overall goal of this grant is to identify novel molecule ligands and receptors that generate the complex and orderly dendrite branches of the nociceptive PVD neurons in C. elegans. Our hypothesis is that interactions between membrane molecules guide dendritic growth and branching in its environment. Following up on our recent discovery of a transmembrane leucine-rich repeat molecule DMA-1 that is essential for PVD dendritic morphogenesis, in specific aim 1, we will further understand the function of DMA-1 by further characterizing its loss-of-function phenotypes, testing its sufficiency and searching for its interaction partners.
In specific aim 2, we will explore the function of cell adhesion L1CAM/SAX-7 in generating patterned dendritic branches. We will examine the loss- and gain-of-function phenotype of sax-7, determine its cellular requirement and examine its subcellular localization. We will also study the function of a novel transmembrane protein W01F3.1, which we isolated from a forward genetic screen.
In specific aim3, we will test if DMA-1, SAX-7 and W01F3.1 form a tripartite ligand-receptor complex that pattern PVD dendrite using genetic and biochemical means.

Public Health Relevance

Dendrites are highly branched neuronal processes that serve as the antenna of neurons to gather information. Understanding the molecular mechanisms underlying dendrite growth and branching will provide the basis for developing new strategies for combating developmental neurological diseases, for slowing down the progression of neurodegenerative diseases. In addition, such knowledge will be helpful for developing strategies to promote the regeneration of neural circuits after stroke.

National Institute of Health (NIH)
National Institute of Neurological Disorders and Stroke (NINDS)
Research Project (R01)
Project #
Application #
Study Section
Special Emphasis Panel (ZRG1-MDCN-E (02))
Program Officer
Mamounas, Laura
Project Start
Project End
Budget Start
Budget End
Support Year
Fiscal Year
Total Cost
Indirect Cost
Stanford University
Schools of Arts and Sciences
United States
Zip Code
Liu, Xianzhuang; Wang, Xiangming; Shen, Kang (2016) Receptor tyrosine phosphatase CLR-1 acts in skin cells to promote sensory dendrite outgrowth. Dev Biol 413:60-9
Dong, Xintong; Chiu, Hui; Park, Yeonhee Jenny et al. (2016) Precise regulation of the guidance receptor DMA-1 by KPC-1/Furin instructs dendritic branching decisions. Elife 5:
Zou, Wei; Shen, Ao; Dong, Xintong et al. (2016) A multi-protein receptor-ligand complex underlies combinatorial dendrite guidance choices in C. elegans. Elife 5:
Wei, Xing; Howell, Audrey S; Dong, Xintong et al. (2015) The unfolded protein response is required for dendrite morphogenesis. Elife 4:e06963
Liang, Xing; Dong, Xintong; Moerman, Donald G et al. (2015) Sarcomeres Pattern Proprioceptive Sensory Dendritic Endings through UNC-52/Perlecan in C. elegans. Dev Cell 33:388-400
Chia, Poh Hui; Li, Pengpeng; Shen, Kang (2013) Cell biology in neuroscience: cellular and molecular mechanisms underlying presynapse formation. J Cell Biol 203:11-22
Dong, Xintong; Liu, Oliver W; Howell, Audrey S et al. (2013) An extracellular adhesion molecule complex patterns dendritic branching and morphogenesis. Cell 155:296-307