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The C. elegans ALA Neuron: Its Transcriptions and Roles in Inducing Sleep

Citation

Chow, Elly Suk Hen (2014) The C. elegans ALA Neuron: Its Transcriptions and Roles in Inducing Sleep. Dissertation (Ph.D.), California Institute of Technology. doi:10.7907/BFB7-Y645. http://resolver.caltech.edu/CaltechTHESIS:06052014-104149263

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Abstract

A long-standing yet to be accomplished task in understanding behavior is to dissect the function of each gene involved in the development and function of a neuron. The C. elegans ALA neuron was chosen in this study for its known function in sleep, an ancient but less understood animal behavior. Single-cell transcriptome profiling identified 8,133 protein-coding genes in the ALA neuron, of which 57 are neuropeptide-coding genes. The most enriched genes are also neuropeptides. In combination with gain-of-function and loss-of-function assays, here I showed that the ALA-enriched FMRFamide neuropeptides, FLP-7, FLP-13, and FLP-24, are sufficient and necessary for inducing C. elegans sleep. These neuropeptides act as neuromodulators through GPCRs, NPR-7, and NPR-22. Further investigation in zebrafish indicates that FMRFamide neuropeptides are sleep-promoting molecules in animals. To correlate the behavioral outputs with genomic context, I constructed a gene regulatory network of the relevant genes controlling C. elegans sleep behavior through EGFR signaling in the ALA neuron. First, I identified an ALA cell-specific motif to conduct a genome-wide search for possible ALA-expressed genes. I then filtered out non ALA-expressed genes by comparing the motif-search genes with ALA transcriptomes from single-cell profiling. In corroborating with ChIP-seq data from modENCODE, I sorted out direct interaction of ALA-expressed transcription factors and differentiation genes in the EGFR sleep regulation pathway. This approach provides a network reference for the molecular regulation of C. elegans sleep behavior, and serves as an entry point for the understanding of functional genomics in animal behaviors.

Item Type:Thesis (Dissertation (Ph.D.))
Subject Keywords:sleep, neuropeptide, C. elegans, genomics
Degree Grantor:California Institute of Technology
Division:Biology and Biological Engineering
Major Option:Biology
Thesis Availability:Public (worldwide access)
Research Advisor(s):
  • Sternberg, Paul W.
Thesis Committee:
  • Prober, David A. (chair)
  • Stathopoulos, Angelike
  • Allman, John Morgan
  • Sternberg, Paul W.
Defense Date:29 May 2014
Record Number:CaltechTHESIS:06052014-104149263
Persistent URL:http://resolver.caltech.edu/CaltechTHESIS:06052014-104149263
DOI:10.7907/BFB7-Y645
Default Usage Policy:No commercial reproduction, distribution, display or performance rights in this work are provided.
ID Code:8485
Collection:CaltechTHESIS
Deposited By: Suk Hen Chow
Deposited On:05 Jun 2014 20:40
Last Modified:11 Apr 2019 17:50

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