We wish to continue our study of genes needed for neuronal differentiation and function in the nematode Caenorhabditis elegans. Most of the research will center, as in the past, on the analysis of the development and activity of a set of six touch receptor neurons (the touch cells). Previous research under this grant has led to the identification of over 500 mutations that render the animal touch insensitive. These mutations define 17 genes needed for the generation, specification, maintenance, and function of the touch cells. Four of these genes and eight others that do not mutate to touch insensitivity act combinatorially in the development of the cells, allowing them to express cell-specific features and restricting their number to six. The remaining genes encode products that are needed for the function of the cells. We have developed a model in which the proteins encoded by twelve of these genes are components or modulators of the mechanosensory apparatus needed by the cells to sense touch. This is the first molecular model for a eukaryotic mechanical sense. In the upcoming grant period we wish to investigate how this combinatorial control specifies touch cell fate, uncover new touch-cell-specific genes, and test predictions of our model of mechanosensation.
The specific aims of the proposal are: 1) to characterize combinatorial regulation of touch cell fate. 2) To identify and characterize new genes needed for touch cell development and function. 3) To continue the molecular genetic characterization of genes whose products are needed for mechanosensation. 4) To investigate the electrophysiological properties of a) wild-type and mutant touch cells in situ and b) touch-cell function proteins in Xenopus oocytes.

Agency
National Institute of Health (NIH)
Institute
National Institute of General Medical Sciences (NIGMS)
Type
Method to Extend Research in Time (MERIT) Award (R37)
Project #
5R37GM030997-19
Application #
6180350
Study Section
Special Emphasis Panel (ZRG1-MDCN-6 (01))
Project Start
1982-08-01
Project End
2004-08-31
Budget Start
2000-09-01
Budget End
2001-08-31
Support Year
19
Fiscal Year
2000
Total Cost
$637,444
Indirect Cost
Name
Columbia University (N.Y.)
Department
Biology
Type
Other Domestic Higher Education
DUNS #
064931884
City
New York
State
NY
Country
United States
Zip Code
10027
Shi, Lingyan; Zheng, Chaogu; Shen, Yihui et al. (2018) Optical imaging of metabolic dynamics in animals. Nat Commun 9:2995
Zheng, Chaogu; Jin, Felix Qiaochu; Trippe, Brian Loeber et al. (2018) Inhibition of cell fate repressors secures the differentiation of the touch receptor neurons of Caenorhabditis elegans. Development 145:
Shi, Shujie; Buck, Teresa M; Kinlough, Carol L et al. (2017) Regulation of the epithelial Na+ channel by paraoxonase-2. J Biol Chem 292:15927-15938
Zheng, Chaogu; Diaz-Cuadros, Margarete; Nguyen, Ken C Q et al. (2017) Distinct effects of tubulin isotype mutations on neurite growth in Caenorhabditis elegans. Mol Biol Cell 28:2786-2801
Chen, Yushu; Bharill, Shashank; Altun, Zeynep et al. (2016) Caenorhabditis elegans paraoxonase-like proteins control the functional expression of DEG/ENaC mechanosensory proteins. Mol Biol Cell 27:1272-85
Chen, Yushu; Bharill, Shashank; O'Hagan, Robert et al. (2016) MEC-10 and MEC-19 Reduce the Neurotoxicity of the MEC-4(d) DEG/ENaC Channel in Caenorhabditis elegans. G3 (Bethesda) 6:1121-30
Zheng, Chaogu; Diaz-Cuadros, Margarete; Chalfie, Martin (2016) GEFs and Rac GTPases control directional specificity of neurite extension along the anterior-posterior axis. Proc Natl Acad Sci U S A 113:6973-8
Chen, Xiaoyin; Cuadros, Margarete Diaz; Chalfie, Martin (2015) Identification of nonviable genes affecting touch sensitivity in Caenorhabditis elegans using neuronally enhanced feeding RNA interference. G3 (Bethesda) 5:467-75
Chen, Xiaoyin; Chalfie, Martin (2015) Regulation of mechanosensation in C. elegans through ubiquitination of the MEC-4 mechanotransduction channel. J Neurosci 35:2200-12
Zheng, Chaogu; Jin, Felix Qiaochu; Chalfie, Martin (2015) Hox Proteins Act as Transcriptional Guarantors to Ensure Terminal Differentiation. Cell Rep 13:1343-1352

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