An apical junction protein antagonizes mechanosensitive calcium signaling to establish stochastic choices of olfactory neuron subtypes

Mechanical forces regulate brain development and left-right body patterning. However, the role of mechanical signaling in brain lateralization remains unclear. In <i>Caenorhabditis elegans</i> , the left and right AWC olfactory neurons communicate via a gap junction network to stochastically differentiate into the default AWC ^OFF and induced AWC ^ON subtypes. SLO BK potassium channels, SLO-1 and SLO-2, act redundantly to inhibit a calcium-regulated protein kinase pathway in the specification of the AWC ^ON subtype. Here, we identified a role for AJM-1 (apical junction molecule 1) in promoting AWC ^ON from an unbiased forward genetic screen for mutants that suppress the <i>slo-1(gf)</i> 2AWC ^ON phenotype. AJM-1 is located at three distinct tight junctions between amphid neurons (including AWC) and sheath glia, sheath and socket glia, and socket glia and hypodermal cells (also known as epidermal cells) at the anterior tip of the animal. In addition to its cell-autonomous function, the non-cell-autonomous function of AJM-1 in glial and hypodermal cells is required for the specification of the AWC ^ON subtype. Furthermore, we identified a role for the DEL-1 mechanosensitive DEG/ENaC channel in the calcium signaling pathway, mediated by UNC-2 and EGL-19 voltage-activated calcium channels, that specifies AWC ^OFF . Together, our results suggest a mechanism in which AJM-1 promotes SLO-1 expression and antagonizes mechanosensitive calcium signaling, thereby promoting the AWC ^ON subtype. This study provides insight into the role of mechanical force in the stochastic lateralization of olfactory neurons.