The developing nervous system generates a large diversity of cell types with distinct patterns of gene expression and functions. One way to establish neuronal diversity is to specify neuronal subtypes across the left-right axis. The C. elegans left and right AWC olfactory neurons communicate to specify asymmetric subtypes, AWCOFF and AWCON. The default AWCOFF is specified by a Ca2+-regulated kinase cascade that is activated by influx of Ca2+ through the voltage-gated Ca2+ channel UNC-2/UNC-36. Intercellular communication between the two AWC neurons and other neurons through the NSY-5/innexin gap junction network antagonizes
unc-2/unc-36 Ca2+ signaling in the induced AWCON cell. Our recent data suggests that voltage- and calcium-activated SLO BK potassium channels
slo-1 and
slo-2 acts redundantly downstream of
nsy-5 to inhibit
unc-2/unc-36 Ca2+ signaling in the specification of AWCON.To identify the genes required for
slo-1 function in inhibiting
unc-2/unc-36 Ca2+ signaling for promoting AWCON, we performed a non-biased forward genetic screen to isolate mok (modifier of K+ channel) mutants that suppress the
slo-1(gf) 2-AWCON-neuron phenotype.
mok-1(
vy11) is one of the mutants identified from this screen. The 2-AWCOFF-neuron phenotype of
mok-1(
vy11) mutants is suppressed by loss-of-function mutations in the Ca2+ channel gene
unc-36, suggesting that
mok-1 acts upstream of the
unc-2/unc-36 Ca2+ signaling pathway. Together, our results suggest a model in which
nsy-5 inhibits
unc-2/unc-36 Ca2+ signaling through
slo-1 and
mok-1. We identified the mutation responsible for the
vy11 phenotype using whole genome sequencing with the help of Alex Boyanov in the Oliver Hobert lab. Further genetic analysis and behavior analysis of the
vy11 mutant, as well as molecular characterization of
mok-1 will be presented in the meeting.