We are interested in understanding signaling pathways that control cell fate in the nervous system. The nematode C. elegans senses volatile odors through three bilaterally symmetric pairs of neurons, AWA, AWB, and AWC. The
str-2 receptor is expressed asymmetrically in only one of the two AWC neurons. Expression of
str-2 is stochastic: fifty percent of animals express
str-2 on the left neuron, and fifty percent express it on the right. Laser ablation experiments and analysis of axon guidance mutants indicate that wild-type axon guidance and probably direct contact between the two AWC neurons are required for normal
str-2 expression (Troemel et al., 1999). Behavioral assays in laser ablated animals indicate that the
str-2-expressing (AWCON) and non
str-2-expressing (AWCOFF) neurons are functionally distinct; they sense different, but overlapping set of odorants (Wes and Bargmann, 2001). To determine the molecular pathway required for establishing AWC asymmetry, we have performed screens for neuronal symmetry (nsy) mutants. A screen for mutants with two AWCON neurons revealed that a calcium-activated MAP kinase cascade represses
str-2 expression in AWC (Sagasti et al., 2001). Genetic epistasis results indicate that
nsy-3 2-AWCON mutants fall upstream of calcium channels in this pathway.
nsy-3 mutations are semi-dominant alleles of
slo-1, a calcium-activated potassium channel (Wang et al., 2001). SLO-1 is located presynaptically in many types of neurons and can colocalize with voltage-gated calcium channels, making it a candidate for direct participation in this pathway. Further characterization is underway. A screen for mutants with two AWCOFF neurons revealed eight genes involved in different aspects of AWC development or maintenance of
str-2 expression. Epistasis experiments indicate that two genes,
nsy-4 and
nsy-5, act upstream of the calcium activated MAP kinase pathway and may be involved in communication between the two AWC neurons. These mutations are currently being further mapped and characterized. Troemel, E., Sagasti, A., and Bargmann, C. (1999). Cell 99, 387-398. Sagasti A, Hisamoto N, Hyodo J, Tanaka-Hino M, Matsumoto K, Bargmann CI. (2001). Cell 105, 221-32; Wang, Z., Saifee, O., Nonet, M., and Salkoff, L. (2001). Neuron 32, 867-881; Wes, P. and Bargmann, C. (2001). Nature 410, 698-701.