With its well-defined neuronal architecture and powerful genetics, C. elegans is a useful model system for studies of neuronal differentiation. In an effort to identify genes that specify motor neuron fate, we screened for mutations that selectively reduce expression of
acr-5 ::YFP in B-class motor neurons. Three of these isolates (
wd55,
wd67,
wd72 ) are new alleles of
rpm-1 (Regulator of Presynaptic Morphology). The RPM-1 protein and its Drosophila homolog, Hiw, are localized to perisynaptic regions adjacent to the active zone. Mutations in
rpm-1/hiw disrupt synaptic structure and function. This effect may result from disregulation of ubiquitin-dependent protein degradation (Liao, Hung et al. 2004) (McCabe, Hom et al. 2004). Genetic epistasis experiments indicate that RPM-1 function depends on downregulation of
pmk-3 (
p38 MAPK) signaling (K. Nakata and Y. Jin, pers. comm.). We have now shown that
pmk-3 also suppresses disregulation of B-class motor neuron markers in
rpm-1 mutants. This finding suggests that RPM-1, a component of the presynaptic apparatus, regulates transcription of specific target genes via a MAPK signaling pathway. We have used the mRNA tagging method (see Von Stetina et al., this meeting) to identify downstream targets of
rpm-1 . We used a pan neural mRNA tagging line ( F25B3.3 ::FLAG::PAB-1) to isolate mRNA from all neurons in the
rpm-1 deletion mutant,
ok364 . From 4 independent data sets, we determined that 443 genes are upregulated and 260 genes are downregulated in
rpm-1 mutant neurons. We are currently testing candidate genes from these lists for roles in RPM-1 function. Liao, E. H., W. Hung, et al. (2004). "An SCF-like ubiquitin ligase complex that controls presynaptic differentiation." Nature. McCabe, B. D., S. Hom, et al. (2004). "Highwire regulates presynaptic BMP signaling essential for synaptic growth." Neuron 41(6): 891-905.