Date of Award
Summer 7-27-2018
Degree Type
Thesis
Degree Name
Master of Science in Integrative Biology (MSIB)
Department
Biology
Major Professor
Martin L. Hudson
First Committee Member
Melanie Griffin
Second Committee Member
Joel McNeal
Third Committee Member
Susan Smith
Abstract
NeuroD1 is a vertebrate helix-loop-helix transcription factor that is involved in nervous system development and pancreatic islet development. NeuroD1 -/- mice is uncoordinated, has seizures and a reduce brain size (Miyata et al. 1999). In C. elegans, the ortholog gene is cnd-1. Hallam et al. 2000, showed that cnd-1 has a role in cell fate determination of GABAergic, DD motor neurons, in addition to a role in axon morphology. cnd-1(ju29) worms, show GABAergic motor neuron defect, they have a “kinky” backward movement phenotype and their axons are branched. However, only three genes are known to be downstream targets of CND-1/HLH-2, unc-3, unc-4 and unc-40. We used a RNA-Seq approach to identify additional genes under the control of CND-1/HLH-2. We found that cnd-1 is up-regulated in ju29, which suggests a negative regulation of itself. Also, we identified two HOX gene transcription factors, ceh-5 and ceh-13, that we predict are under the control of CND-1/HLH-2 and are involve in the axis patterning of the nervous system. Similarly, we predict that cnd-1 has a role as a cell fate reinforcer of sensory and motor neurons; it does this by activating and/or repressing different genes such as srw-85 and rpm-1, in a tissue specific manner. By using an integrative approached we identified new downstream targets of CND-1/HLH2 and assembled a more comprehensive gene regulatory network. Surprisingly, our results also suggest that cnd-1 might be involve in the conservation of a food homeostasis pathway, that might be similar to that observed in vertebrates, suggesting that cnd-1 has additional roles to nervous system development.