Neuronal cell body and growth cone migrations shape the overall pattern and connectivity of nervous systems. The objective of the proposed research is to investigate the mechanisms that control neuronal migrations. Understanding these basic mechanisms could lead to insights into how damaged nervous systems might be repaired. The application has four specific aims. To determine whether EGL-20 Wnt acts as a guidance cue for the HSN. The migrations of the HSN motor neuron require the Wnt homolog EGL-20, and preliminary experiments suggest that EGL-20 acts as a guidance cue, a novel activity for a Wnt. To determine whether EGL-20 guides the HSNs to their destinations, EGL-20 will be misexpressed. Downstream components in EGL-20 Wnt will be identified to determine whether they act in the HSN. 1. To determine how the CAM-1 Ror kinase antagonizes EGL-20 in HSN migration. Genetic interactions between the egl-20 and cam-1 mutations indicate that these genes antagonize each other in HSN migration. CAM-1 could alter the distribution of EGL-20 by directly binding to EGL-20. Alternatively, CAM-1 could encode a component of a separate signaling pathway that antagonizes EGL-20. A series of genetic and molecular experiments are proposed to distinguish between these hypotheses. 2. To further characterize the role of Abelson oncogene ABL-1 in cell migration and identify genes that act in the ABL-1 pathway. The Abelson oncogene plays a central role in the growth cone migrations of other organisms. In C. elegans, ABL-1, like CAM-1, antagonizes the activity of EGL-20 in HSN migration. Experiments are proposed to determine which portions of ABL-1 function in migration, to determine where ABL-1 functions, and to identify molecules that act with ABL-1. 3. To define the roles of VAB-8/UNC-51 interactions in cell and growth cone migrations. VAB-8 interacts physically with the conserved serine/threonine kinase UNC-51. Preliminary experiments also suggest that UNC-51 can phosphorylate VAB-8L. The functional significance of the VAB-8/UNC-51 interactions and the role of VAB-8 phosphorylation will be tested.

Agency
National Institute of Health (NIH)
Institute
National Institute of Neurological Disorders and Stroke (NINDS)
Type
Research Project (R01)
Project #
5R01NS032057-13
Application #
7027638
Study Section
Molecular, Cellular and Developmental Neurosciences 2 (MDCN)
Program Officer
Leblanc, Gabrielle G
Project Start
1994-04-01
Project End
2007-02-28
Budget Start
2006-03-01
Budget End
2007-02-28
Support Year
13
Fiscal Year
2006
Total Cost
$346,587
Indirect Cost
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
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
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
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
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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