The basic helix-loop-helix transcription factor NeuroD1 is deeply conserved across phyla, and plays a crucial role in cell fate specification in both the vertebrate nervous system and pancreas. Defects in NeuroD1 function have been linked to chronic seizures and maturity onset diabetes of the young. Despite this, the downstream transcriptional targets of NeuroD1 have not been well characterized. 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 used a comparative transcriptome approach to understand the role of
cnd-1, the C. elegans ortholog of NeuroD1, during embryonic nervous system development and function. 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. 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.