ngn-1/neurogenin Activates Transcription of Multiple Terminal Selector Transcription Factors in the Caenorhabditis elegans Nervous System

Abstract

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. Understanding the gene regulatory networks that orchestrate neural development, specifically cascades of proneural transcription factors, can better elucidate which genes are most important during early neurogenesis. Neurogenins are a family of deeply conserved factors shown to be both necessary and sufficient for the development of neural subtypes. However, the immediate downstream targets of neurogenin are not well characterized. The objective of this study was to further elucidate the role of /neurogenin in nervous system development and to identify its downstream transcriptional targets, using the nematode Caenorhabditis elegans as a model for this work. We found that is required for axon outgrowth, nerve ring architecture, and neuronal cell fate specification. We also showed that may have roles in neuroblast migration and epithelial integrity during embryonic development. Using RNA sequencing and comparative transcriptome analysis, we identified eight transcription factors (/NPAS1, /PROP1, /PHOX2A, /LHX6, /NR2E3, /LHX1, /ZNF503, and /RORB) whose transcription is activated, either directly or indirectly, by . Our results show that has a role in transcribing known terminal regulators that establish and maintain cell fate of differentiated neural subtypes and confirms that functions as a proneural transcription factor in C. elegans neurogenesis.