Understanding how neuroblasts and neurons polarize is a fundamental problem in neurodevelopment. We propose to study this problem in C. elegans with a focus on how polarity is established along the C. elegans anterior/posterior (A/P) axis. C. elegans has been an important model for the nervous system development. In both C. elegans and the spinal cord, the same molecules guide migrating axons along the dorsal/ventral and A/P axes. Wnt glycoproteins, for example, guide axons toward the anterior in both organisms. In C. elegans, Wnts are the main regulators not only of axon guidance, but also of neuroblast and neuronal polarity. We propose to define the common mechanisms that Wnts use to regulate these two processes. In addition, disregulation of Wnt-pathway components contributes to many forms of cancer. Understanding the mechanisms of Wnt regulation and signaling has potential implications for spinal cord repair and cancer.

Public Health Relevance

All cells exhibit polarity. Polarity is particularly important during nervous system development, where the proper establishment of polarity is essential for neuroblasts to divide to produce neurons, for neurons to migrate and for axons to find their synaptic targets. We propose to study how neuronal polarity is regulated in model organism C. elegans by the family of secreted Wnt glycoproteins.

Agency
National Institute of Health (NIH)
Institute
National Institute of Neurological Disorders and Stroke (NINDS)
Type
Research Project (R01)
Project #
5R01NS032057-21
Application #
8628186
Study Section
Special Emphasis Panel (ZRG1-MDCN-A (05))
Program Officer
Riddle, Robert D
Project Start
1994-04-01
Project End
2016-02-29
Budget Start
2014-03-01
Budget End
2015-02-28
Support Year
21
Fiscal Year
2014
Total Cost
$325,361
Indirect Cost
$108,798
Name
University of California Berkeley
Department
Biochemistry
Type
Schools of Arts and Sciences
DUNS #
124726725
City
Berkeley
State
CA
Country
United States
Zip Code
94704
Chien, Shih-Chieh Jason; Gurling, Mark; Kim, Changsung et al. (2015) Autonomous and nonautonomous regulation of Wnt-mediated neuronal polarity by the C. elegans Ror kinase CAM-1. Dev Biol 404:55-65
Hsu, Jiun-Min; Chen, Chun-Hao; Chen, Yen-Chih et al. (2014) Genetic analysis of a novel tubulin mutation that redirects synaptic vesicle targeting and causes neurite degeneration in C. elegans. PLoS Genet 10:e1004715
Kim, Hon-Song; Kitano, Yuko; Mori, Masataka et al. (2014) The novel secreted factor MIG-18 acts with MIG-17/ADAMTS to control cell migration in Caenorhabditis elegans. Genetics 196:471-9
Teuliere, Jerome; Cordes, Shaun; Singhvi, Aakanksha et al. (2014) Asymmetric neuroblast divisions producing apoptotic cells require the cytohesin GRP-1 in Caenorhabditis elegans. Genetics 198:229-47
Gurling, Mark; Talavera, Karla; Garriga, Gian (2014) The DEP domain-containing protein TOE-2 promotes apoptosis in the Q lineage of C. elegans through two distinct mechanisms. Development 141:2724-34
Weinberg, Peter; Flames, Nuria; Sawa, Hitoshi et al. (2013) The SWI/SNF chromatin remodeling complex selectively affects multiple aspects of serotonergic neuron differentiation. Genetics 194:189-98
Chien, Shih-Chieh; Brinkmann, Eva-Maria; Teuliere, Jerome et al. (2013) Caenorhabditis elegans PIG-1/MELK acts in a conserved PAR-4/LKB1 polarity pathway to promote asymmetric neuroblast divisions. Genetics 193:897-909
Ikegami, Richard; Simokat, Kristin; Zheng, Hong et al. (2012) Semaphorin and Eph receptor signaling guide a series of cell movements for ventral enclosure in C. elegans. Curr Biol 22:1-11
Najarro, Elvis Huarcaya; Wong, Lianna; Zhen, Mei et al. (2012) Caenorhabditis elegans flamingo cadherin fmi-1 regulates GABAergic neuronal development. J Neurosci 32:4196-211
Teulière, Jérôme; Gally, Christelle; Garriga, Gian et al. (2011) MIG-15 and ERM-1 promote growth cone directional migration in parallel to UNC-116 and WVE-1. Development 138:4475-85

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