Date of Award
Master of Science in Integrative Biology (MSIB)
Martin L. Hudson
First Committee Member
Second Committee Member
Third Committee Member
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.
Available for download on Wednesday, August 16, 2023