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.
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.
|Schurek, Eva-Maria; Völker, Linus A; Tax, Judit et al. (2014) A disease-causing mutation illuminates the protein membrane topology of the kidney-expressed prohibitin homology (PHB) domain protein podocin. J Biol Chem 289:11262-71|
|Chen, Xiaoyin; Chalfie, Martin (2014) Modulation of C. elegans touch sensitivity is integrated at multiple levels. J Neurosci 34:6522-36|
|Chalfie, Martin; Hart, Anne C; Rankin, Catharine H et al. (2014) Assaying mechanosensation. WormBook :|
|Topalidou, Irini; van Oudenaarden, Alexander; Chalfie, Martin (2011) Caenorhabditis elegans aristaless/Arx gene alr-1 restricts variable gene expression. Proc Natl Acad Sci U S A 108:4063-8|
|Arnadottir, Johanna; O'Hagan, Robert; Chen, Yushu et al. (2011) The DEG/ENaC protein MEC-10 regulates the transduction channel complex in Caenorhabditis elegans touch receptor neurons. J Neurosci 31:12695-704|
|Topalidou, Irini; Chalfie, Martin (2011) Shared gene expression in distinct neurons expressing common selector genes. Proc Natl Acad Sci U S A 108:19258-63|
|Bounoutas, Alexander; Kratz, John; Emtage, Lesley et al. (2011) Microtubule depolymerization in Caenorhabditis elegans touch receptor neurons reduces gene expression through a p38 MAPK pathway. Proc Natl Acad Sci U S A 108:3982-7|
|Calixto, Andrea; Ma, Charles; Chalfie, Martin (2010) Conditional gene expression and RNAi using MEC-8-dependent splicing in C. elegans. Nat Methods 7:407-11|
|Arnadóttir, Jóhanna; Chalfie, Martin (2010) Eukaryotic mechanosensitive channels. Annu Rev Biophys 39:111-37|
|Bounoutas, Alexander; Zheng, Qun; Nonet, Michael L et al. (2009) mec-15 encodes an F-box protein required for touch receptor neuron mechanosensation, synapse formation and development. Genetics 183:607-17, 1SI-4SI|
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