C-terminal binding proteins (CtBPs) are transcriptional co-repressors which are conserved across many species, including the model organism Caenorhabditis elegans. C. elegans CTBP-1 is expressed in both the nervous system and hypodermis, and regulates several processes, including lifespan. We previously identified defective exploration behaviour and abnormal axonal morphology of dorsal SMD (SMDD) neurons in developing and adult ctbp-1 mutant animals, highlighting a role for CTBP-1 in the development and maintenance of the nervous system. Further characterisation of the morphology of SMDD axons revealed that ctbp-1 mutant animals display longer axons than wild-type animals, suggesting that axon guidance and/or termination cues are disrupted.

From the single C. elegans ctbp-1 locus, two isoforms are transcribed: ctbp-1a and ctbp-1b. These transcripts encode distinct proteins: CTBP-1a, which contains an additional Thanatos-associated protein (THAP) domain, and CTBP-1b. We set out to further understand the function of the two CTBP-1 isoforms in the nervous system. The Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR)- CRISPR Associated Protein 9 (Cas9) system was used to generate a null mutant that removes the function of both CTBP-1a and CTBP-1b, and a mutant that only removes the function of CTBP-1b. The abnormal SMDD morphology and defective exploration behaviour of CTBP-1a mutant animals is not observed in CTBP-1b mutant animals. Furthermore, null mutant animals display the same defective axonal morphology and defective exploration behaviour as the CTBP-1a mutant animals, suggesting that CTBP-1b is not involved in these processes.

Overall, these results demonstrate differential roles for CTBP-1a and CTBP-1b in the regulation of SMDD axonal morphology and exploration behaviour in C. elegans. Further roles for CTBP-1 in the nervous system are being investigated.