Activity and stress during a critical period regulate olfactory sensory neuron differentiation

Abstract

Here, we reveal that the regulation of Drosophila odorant receptor (OR) expression during the pupal stage is permissive and imprecise. We found that olfactory sensory neuron activity directly after hatching both directs and refines OR expression. We demonstrate that, as in mice, dLsd1 and Su(var)3-9 balance heterochromatin formation to direct OR expression. Neuronal activity induces dLsd1 and Su(var)3-9 expression, linking neuronal activity to OR expression. OR expression refinement shows a restricted duration, suggesting a gene regulatory critical period brings olfactory sensory neuron differentiation to an end. Consistent with a change in differentiation, stress during the critical period represses dLsd1 and Su(var)3-9 expression and makes the early permissive OR expression permanent. This induced permissive gene regulatory state makes OR expression resilient to stress later in life. Hence, during a critical period, OR activity feedback similar to in mouse OR selection, defines adult OR expression in Drosophila.

Odor response adaptation in Drosophila—a continuous individualization process

“…1d) and another that adjusts OR levels (Fig. 1e, Table 1, Devaud et al 2001;Golovin et al 2019;Jafari and Alenius 2020).…”

“…OR expression in Drosophila is generally considered a static (Imai et al 2010), predetermined process, but there is considerable plasticity in the levels of OR, GR, and IR expression in the antenna for the first 2 days of an adult fly's life (Jafari and Alenius 2020). This chemoreceptor expression plasticity also fulfills the criteria for a critical period.…”

“…This indicates a direct competition between ORs in the regulation of their expression. Interestingly, activity regulates odorant-responsive and pheromone-responsive OSNs differently (Jafari and Alenius 2020). OR expression is also stress-sensitive, with the stress-induced changes becoming permanent if the stress lasts beyond the critical period.…”

“…The mechanisms underlying the OR gene regulatory critical period build on heterochromatin regulation in ways that are similar to the OR choice mechanism in mouse olfactory neurons (Jafari and Alenius 2020;Monahan and Lomvardas 2015). In non-OSNs in Drosophila, OR genes are embedded in heterochromatin marked with H3K9me3 produced by Su(var)3-9, which prevents OR expression (Gonzalez et al 2019;Jafari and Alenius 2015;Sim et al 2012).…”

“…Consistent with this, the H3K9me3 erasing enzyme Kdm4b, which open heterochromatin, initiates OR expression. A second enzyme, dLsd1, removes the remaining H3K9 methylation and further establishes OR expression (Jafari and Alenius 2020). OR activity induces and balances these enzymes to modulate OR expression (Fig.…”