Date of Award
Summer 8-2-2022
Degree Type
Thesis
Degree Name
Master of Science in Integrative Biology (MSIB)
Department
Biology
Committee Chair/First Advisor
Erica Holliday
Major Professor
Martin Hudson
Second Committee Member
Melanie Griffin
Abstract
A detailed understanding of how the central nervous system (CNS) is formed and connects during early development can provide information on how to understand and treat disease progression associated with CNS dysregulation. Neurodevelopmental disorders are often reported to be polygenetic in nature, leading to conclude that transcription factors may be a key role in the prognosis of such psychiatric complications. Transcription factors are a class of proteins that enhance or suppress gene transcription and can affect a multitude if genetic targets. Neurogenins (Ngns) are a class of deeply conserved basic-helix-loop-helix transcription factor required for fate specification of multiple neuron types and brain structures. Despite its importance in nervous system development and function, the immediate downstream targets of neurogenin are not well characterized. The nematode Caenorhabditis elegans contains a single ngn-1/neurogenin ortholog. ngn-1(ok2200) null mutants show multiple neurological phenotypes, including axon outgrowth defects and embryonic lethality. Previous work in our lab performed RNAseq transcriptomic studies to better understand the role of ngn-1/neurogenin in development. This revealed genetic targets whose expression levels were significantly altered in ngn-1 mutants (Chrestensen et al. 2020). The current work set out to validate a subset of candidate ngn-1 targets by examining GFP-marker genes of gcy-5, gcy-7, glr-6, and lad-2 in wild type and ngn-1(ok2200) mutant backgrounds. gcy-5, gcy-7, and lad-2 are expressed in sensory neurons, whereas glr-6 is expressed in the RIA interneuron. Preliminary data reveals that ngn-1 is required for correct sensory neuron morphology and may have a role in fate determination of the RIA interneuron. Together, these data add further evidence that ngn-1 functions broadly as a proneural transcription factor during C. elegans neurogenesis.