Semester of Graduation
Summer 2026
Degree Type
Thesis
Degree Name
Master of Science in Integrative Biology
Department
Molecular and Cellular Biology - College of Science and Mathematics
Committee Chair/First Advisor
Martin L. Hudson
Second Advisor
Nicholas Green
Third Advisor
Scott Nowak
Abstract
The homeodomain transcription factor NKX2-1 serves a critical role in regulating brain development and function. Heterozygous mutations in Nkx2.1 have been linked to the development of Attention Deficit Hyperactivity Disorder and related neurodevelopmental conditions such as Benign Hereditary Chorea. The regulatory environment downstream of this gene is largely undescribed, creating an imperative for further study. Nkx2.1 is strongly conserved across phyla, allowing us to examine its impact in a simple model organism, the nematode Caenorhabditis elegans. The C. elegans ortholog of Nkx2.1, ceh-27, is a homeobox gene expressed in several tissues including the intestine, pharynx, and many neuron subtypes (McKay et al. 2003; Packer et al. 2019; Taylor et al. 2021). The developmental role of ceh-27 remains uncharacterized. Through genetic manipulation and 4D timelapse confocal microscopy, we found that ceh-27 is required for embryogenesis and specification of multiple neurons by regulating genes required for neuron fate or function. ceh-27 regulates ttx-3, ceh-10, and ngn-1 expression to drive AIY interneuron fate. In addition, ceh-27 is required for ceh-28 expression in the M4 motor neuron and tbh-1 expression in the RIC interneuron. A promoter-driven ceh-27 fluorophore indicates ceh-27 itself is partly regulated through a mechanism of autorepression. Single-cell RNA sequencing of ceh-27 homozygous mutant cells and controls reveals candidate genes under ceh-27 transcriptional regulation associated with several developmental processes including transcriptional regulation, axon guidance, and pharynx, cuticle, and arcade cell development. These transcriptional targets highlight the crucial role ceh-27/Nkx2.1 plays in directing multiple developmental processes during C. elegans embryogenesis.
Comments
Dr. Dongyu Jia, Kennesaw State University, and Dr. Zachary Mielko, Georgia Highlands College, also served as members of this thesis committee.
Funded by NIH grants R15GM140472, R15NS141048, and T32GM150548-03