Neuronal specification and differentiation are orchestrated through signaling molecules and transcription factors. However, the mechanisms underlying how specific transcription factors regulate cell fate are not fully understood. Using C. elegans as a model system, we are investigating the molecular and cellular mechanisms for neuronal cell-fate specification. In C. elegans, the SAA cholinergic interneurons consist of two dorsal (SAADL/R) and two ventral (SAAVL/R) neurons that have been implicated in head foraging via the circuit comprising the RME and SMB motor neurons (White et al., 1986). To examine how the SAA neurons are specified during development, we conducted genetic screens and candidate gene searches utilizing the expression pattern of the
flp-7 neuropeptide gene, which is expressed in the SAA neurons as well as other neurons (Kim et al., 2004). We found that in
unc-42 mutant animals
flp-7 expression was completely abolished only in the SAA neurons, suggesting that
unc-42 is required for the expression of
flp-7 in these neurons. UNC-42 is a paired-like homeodomain protein of the Q50 class homologous to murine Pax-7 (Basch et al. 2006; Baran et al., 1999). To investigate how UNC-42 regulates
flp-7 expression in SAA, we examined the promoter of
flp-7 gene and identified a cis-regulatory motif that is required for
flp-7 expression in SAA. In addition, the promoters of other SAA markers, including
lad-2 (L1 CAM adhesion molecule homolog), are being analyzed. We are also testing whether expression of
unc-42 is autoregulated and whether transgenic worms expressing
unc-42 cDNA under the control of
hsp-16.2 heat shock promoter restores
flp-7 expression in SAA. Finally, we are planning to do further genetic screens to identify other novel genes that control SAA specification.