We will 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 the six touch receptor neurons (TRNs). Previous research under this grant has identified genes needed for the generation, specification, maintenance and function of the TRNs. In particular in the last funding period we enlarged the collection of TRN-expressed genes 8-fold to approximately 200 genes, identified components that restrict TRN development to six cells, and identified the transduction complex that sense touch in these cells. This last complex is the first transduction complex to be identified in any eukaryotic mechanosensory neuron. We also developed several new methods that we will exploit in the upcoming funding period. In particular we will investigate how cell fate is determined and maintained and how the lipid bilayer and extracellular matrix affect mechanosensation.
The specific aims of the proposal are: 1) to investigate the regulation of post-mitotic gene expression, particular examining how genes needed only early in development of neurons are turned off;2) to investigate the basis of cell-type specification within the TRNs;3) to characterize lipid- binding and modulating components of the MEC-4 channel complex and similar proteins;and 4) to investigate the role of the extracellular matrix (ECM) in touch sensitivity. A secondary consequence of the proposed experiments will be the discovery a wealth of genes needed for general development and function of the C. elegans nervous system.

Public Health Relevance

We study the genetic control of nerve cell development and function of touch sensory cells in the nematode Caenorhabditis elegans. Many of the genes we study have counterparts in humans (some being the basis of inherited diseases), but we can study their function much better in this organism. By identifying molecules needed for nerve growth and mechanosensitivity, we gain basic knowledge that is useful in the general understanding of human biology and health, as evident, e.g., by researchers studying the sensing of blood pressure using our molecular models to guide their research.

Agency
National Institute of Health (NIH)
Institute
National Institute of General Medical Sciences (NIGMS)
Type
Research Project (R01)
Project #
2R01GM030997-28
Application #
7783062
Study Section
Neurodifferentiation, Plasticity, and Regeneration Study Section (NDPR)
Program Officer
Tompkins, Laurie
Project Start
1982-08-01
Project End
2013-11-30
Budget Start
2009-12-15
Budget End
2010-11-30
Support Year
28
Fiscal Year
2010
Total Cost
$850,268
Indirect Cost
Name
Columbia University (N.Y.)
Department
Biology
Type
Other Domestic Higher Education
DUNS #
049179401
City
New York
State
NY
Country
United States
Zip Code
10027
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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
Zheng, Chaogu; Chalfie, Martin (2016) Securing Neuronal Cell Fate in C. elegans. Curr Top Dev Biol 116:167-80
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
Zheng, Chaogu; Jin, Felix Qiaochu; Chalfie, Martin (2015) Hox Proteins Act as Transcriptional Guarantors to Ensure Terminal Differentiation. Cell Rep 13:1343-1352
Zheng, Chaogu; Diaz-Cuadros, Margarete; Chalfie, Martin (2015) Hox Genes Promote Neuronal Subtype Diversification through Posterior Induction in Caenorhabditis elegans. Neuron 88:514-27
Chen, Xiaoyin; Chalfie, Martin (2015) Regulation of mechanosensation in C. elegans through ubiquitination of the MEC-4 mechanotransduction channel. J Neurosci 35:2200-12

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