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.

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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.

National Institute of Health (NIH)
National Institute of Neurological Disorders and Stroke (NINDS)
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Special Emphasis Panel (ZRG1-MDCN-A (05))
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Riddle, Robert D
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University of California Berkeley
Schools of Arts and Sciences
United States
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Teuliere, Jerome; Kovacevic, Ismar; Bao, Zhirong et al. (2018) The Caenorhabditis elegans gene ham-1 regulates daughter cell size asymmetry primarily in divisions that produce a small anterior daughter cell. PLoS One 13:e0195855
Teuliere, Jerome; Garriga, Gian (2017) Size Matters: How C. elegans Asymmetric Divisions Regulate Apoptosis. Results Probl Cell Differ 61:141-163
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
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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
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
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

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