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.

National Institute of Health (NIH)
National Institute of General Medical Sciences (NIGMS)
Research Project (R01)
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Neurodifferentiation, Plasticity, and Regeneration Study Section (NDPR)
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Sesma, Michael A
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Columbia University (N.Y.)
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New York
United States
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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, 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
Zheng, Chaogu; Chalfie, Martin (2016) Securing Neuronal Cell Fate in C. elegans. Curr Top Dev Biol 116:167-80
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
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, Yushu; Bharill, Shashank; Isacoff, Ehud Y et al. (2015) Subunit composition of a DEG/ENaC mechanosensory channel of Caenorhabditis elegans. Proc Natl Acad Sci U S A 112:11690-5
Zheng, Chaogu; Diaz-Cuadros, Margarete; Chalfie, Martin (2015) Hox Genes Promote Neuronal Subtype Diversification through Posterior Induction in Caenorhabditis elegans. Neuron 88:514-27
Kelley, Melissa; Yochem, John; Krieg, Michael et al. (2015) FBN-1, a fibrillin-related protein, is required for resistance of the epidermis to mechanical deformation during C. elegans embryogenesis. Elife 4:
Zheng, Chaogu; Diaz-Cuadros, Margarete; Chalfie, Martin (2015) Dishevelled attenuates the repelling activity of Wnt signaling during neurite outgrowth in Caenorhabditis elegans. Proc Natl Acad Sci U S A 112:13243-8
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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