Unraveling the neurogenin/ngn-1 gene regulatory network of C. elegans using classical genetics and comparative transcriptomics

<p>Proper nervous system development is required for an organism’s survival and function. Defects in neurogenesis have been linked to neurodevelopmental disorders such as schizophrenia and autism spectrum disorders. Understanding the gene regulatory networks that orchestrate neural development, specifically cascades of proneural transcription factors, can better elucidate which genes are most essential in governing early neurogenesis. Neurogenins are a family of such factors that are both sufficient and necessary for the development of neural sub-types in mice, primarily through the regulation of other factors, particularly NeuroD. The objective of this study was to evaluate previously established regulatory targets of neurogenin(<em>ngn-1</em>) and to identify unknown downstream targets, using the nematode <em>Caenorhabditis elegans</em> as a model for these studies. We find that in <em>C. elegans,</em> neurogenin is required for axon outgrowth, cell fate specification, and epithelial integrity during embryonic development. Using RNA sequencing and comparative transcriptome analysis we found that <em>ngn-1</em> acts primarily to repress transcription, facilitating proper embryogenesis. We also identified specific candidates for activation by <em>ngn-1</em>, including <em>hlh-34</em>(NPAS1) and <em>unc-42</em>(Prop1), which we further validated using genetic methods. Our results identify novel pathways connecting <em>ngn-1</em> to known terminal regulators, which maintain cell fate of terminally differentiated neural subtypes, and align neurogenins within the larger context of proneural transcription factors.</p>

Name thesis:degree_name

Master of Science in Integrative Biology (MSIB)

Level thesis:degree_level

Thesis

Discipline thesis:degree_discipline

Biology

Year dc:date.available

2019

Author dc:creator

• Christensen, Elyse

Contributors dc:contributor

• Scott Nowak
• Jared Taglialatela

• neurogenin
• ngn-1
• neurodevelopment
• transcription factor
• bHLH
• transcriptome
• Biology
• Genetics
• Integrative Biology

Repository record dc:identifier

https://digitalcommons.kennesaw.edu/integrbiol_etd/45

OAI identifier oai:identifier

oai:digitalcommons.kennesaw.edu:integrbiol_etd-1046