The CaMKII UNC-43 activates the MAPKKK NSY-1 to execute a lateral signaling decision required for asymmetric olfactory neuron fates

A stochastic cell fate decision mediated by axon contact and calcium signal ing causes one of the two bilaterally symmetric AWC neurons, either AWCL or AWCR, to express the candidate olfactory receptor str-2 nsy-1 mutants expr ess str-2 in both neurons, disrupting AWC asymmetry, nsy-1 encodes a homolo g of the human MAP kinase kinase kinase (MAPKKK) ASK1, an activator of JNK and p38 kinases. Based on genetic epistasis analysis, nsy-1 appears to act downstream of the CaMKII unc-43, and NSY-1 associates with UNC-43, suggesti ng that UNC-43/CaMKII activates the NSY-1 MAP kinase cassette. Mosaic analy sis demonstrates that UNC-43 and NSY-1 act primarily in a cell-autonomous e xecution step that represses str-2 expression in one AWC cell, downstream o f the initial lateral signaling pathway that coordinates the fates of the t wo cells.