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Abstract

Although we have made progress in identifying gross differences between nervous system function and organization across species, what remains to be discovered is whether there are conserved molecular factors that drive these evolutionary changes. We aim to answer this question by comparing cell fate specification in the nervous systems of two distantly related nematode species, Caenorhabditis elegans (Cel) and Pristionchus pacificus (Ppa). Using CRISPR, we have engineered null mutations in a se- ries of transcription factors that have been well-characterized as terminal selectors, or master regulators of neuronal fate in Cel. These include unc-42, unc-3, unc-4, unc-30, vab-7, mec-3, and unc-86, which have all been shown to regulate the identity of neu- rons important for locomotion and sensation in Cel. Most of the Ppa orthologs of these genes show conservation of their roles in nematode behavior, namely locomotion and sensation of mechanosensory or nociceptive cues. (Some of these genes, for which we have epitope-tagged strains, also show identical or similar expression patterns.) Others, like unc-30, show divergence in their terminal selector roles: in Ppa-unc-30, GABA identity in the Ventral Nerve Cord (VNC) is retained, rather than lost, and mutant animals do not “shrink”, which is expected when GABA is absent from the VNC. Together, these comparative analyses allow us to not only characterize neuronal fate specification in a new model organism, but also investigate how this specification is conserved across species in some areas of the nervous system while in others it may have diverged.