C. elegans cnd-1/NeuroD1 functions with the Hox gene ceh-13/labial to control multiple genes required for nervous system development and function

Identifying the mechanisms behind neuronal fate specification are key to understanding neurodevelopmental disorders such as autism and schizophrenia. In vivo nervous system fate specification is difficult to study in vertebrates. However, the nematode Caenorhabditis elegans, with its invariant cell lineage and simple nervous system of 302 neurons, is an ideal organism to explore the earliest stages of neural development. We took a comparative transcriptome approach to understanding the role of cnd-1/NeuroD1 in C. elegans nervous system development and function. This basic helix-loop-helix transcription factor is deeply conserved across phyla, and plays a crucial role in cell fate specification in both the vertebrate nervous system and pancreas. We find that cnd-1 partially represses its own expression during C. elegans embryogenesis. In addition, we show that cnd-1 controls the expression of ceh-5, a Vax2-like homeobox class transcription factor expressed in the nervous system and in head muscles. We also demonstrate a role for the Hox gene ceh-13/labial in defining the fate of cnd-1-expressing motorneurons. Finally, we show that cnd-1 also controls the expression levels of genes required for post-mitotic function, including the RING-finger ubiquitin ligase rpm-1. These data highlight the utility of comparative transcriptomes for understanding the nuances of transcription factor control, and establish a paradigm for future transcriptome-based studies. RNAseq analysis of Caenorhabditis elegans embryogenesis in N2 wild type (n = 3) and cnd-1(ju29) mutants (n = 3)