Genetic analysis of cGMP-dependent chemosensory signal transduction pathways in the detection of bacterial metabolites by C. elegans

The ability of metazoans to sense and interpret the external chemical environment is conferred by the chemosensory nervous system governing the senses of smell and taste. Chemosensory neurons convey external stimuli in the form of electrical impulses, as well as by changes in gene expression. This thesis describes the genetic elucidation of a Caenorhabditis elegans molecular pathway that transduces the presence of pathogens to activate the transcription of a neuroendocrine ligand. Previously, our group has showed that secondary metabolites produced by the pathogen P. aeruginosa cause an expression pattern change of the gene coding for the C. elegans TGF-beta ligand DAF-7. Using forward and reverse genetic approaches, we identified several cGMP-related components that are essential for the pathway, including a subunit for cyclic nucleotide-gated channels, CNG-2, and a cGMP-dependent kinase, EGL-4. We show that while CNG-2 induces daf-7 expression in a calcium-dependent manner, EGL-4 likely works in a calcium-independent manner to regulate daf-7 expression. Our data suggest that EGL-4 acts by selectively promoting the transcription of neuronal genes in response to appropriate stimuli. In a separate set of experiments, we also showed that the expression of daf-7 is discretely regulated by different classes of intraflagellar transport proteins that function in cilia.

Name thesis:degree_name

Doctoral

Department dc:contributor.department

Massachusetts Institute of Technology. Department of Biology

Grantor dc:publisher

Massachusetts Institute of Technology

Year dc:date.issued

2019

Author dc:creator

• Park, Jaeseok,Ph.D.Massachusetts Institute of Technology.

Advisor dc:contributor.advisor

• Dennis H. Kim.

• Biology.

Statement dc:rights

• MIT theses are protected by copyright. They may be viewed, downloaded, or printed from this source but further reproduction or distribution in any format is prohibited without written permission.

Licence dc:rights.uri

• http://dspace.mit.edu/handle/1721.1/7582

Language dc:language.iso

eng

Handle dc:identifier.uri

https://hdl.handle.net/1721.1/123717

OAI identifier oai:identifier

oai:dspace.mit.edu:1721.1/123717