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 #
5R01NS032057-19
Application #
8239935
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
2012-03-01
Budget End
2013-02-28
Support Year
19
Fiscal Year
2012
Total Cost
$329,885
Indirect Cost
$111,135
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
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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
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Singhvi, Aakanksha; Teuliere, Jerome; Talavera, Karla et al. (2011) The Arf GAP CNT-2 regulates the apoptotic fate in C. elegans asymmetric neuroblast divisions. Curr Biol 21:948-54
Babu, Kavita; Hu, Zhitao; Chien, Shih-Chieh et al. (2011) The immunoglobulin super family protein RIG-3 prevents synaptic potentiation and regulates Wnt signaling. Neuron 71:103-16
Steimel, Andreas; Wong, Lianna; Najarro, Elvis Huarcaya et al. (2010) The Flamingo ortholog FMI-1 controls pioneer-dependent navigation of follower axons in C. elegans. Development 137:3663-73
Fleming, Tinya; Chien, Shih-Chieh; Vanderzalm, Pamela J et al. (2010) The role of C. elegans Ena/VASP homolog UNC-34 in neuronal polarity and motility. Dev Biol 344:94-106
Vanderzalm, Pamela J; Pandey, Amita; Hurwitz, Michael E et al. (2009) C. elegans CARMIL negatively regulates UNC-73/Trio function during neuronal development. Development 136:1201-10

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