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.

Agency
National Institute of Health (NIH)
Institute
National Institute of Neurological Disorders and Stroke (NINDS)
Type
Research Project (R01)
Project #
5R01NS082208-02
Application #
8659526
Study Section
Special Emphasis Panel (ZRG1-MDCN-E (02))
Program Officer
Mamounas, Laura
Project Start
2013-06-01
Project End
2018-05-31
Budget Start
2014-06-01
Budget End
2015-05-31
Support Year
2
Fiscal Year
2014
Total Cost
$333,313
Indirect Cost
$116,750
Name
Stanford University
Department
Biology
Type
Schools of Arts and Sciences
DUNS #
009214214
City
Stanford
State
CA
Country
United States
Zip Code
94305
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