Environmental stress early in development can impact adult phenotypes through programmed changes in gene expression. C. elegans larvae respond to environmental stress by entering the alternative dauer diapause pathway, and resume development once conditions improve (postdauers). Our previous work showed that postdauer adults retain a cellular memory of their developmental history through changes in gene expression, genome-wide chromatin states, small RNA profiles, and life history traits when compared to animals that bypassed the dauer stage (controls). However, little is known about the mechanisms that establish and maintain these changes in response to developmental history. We have identified the osm-9 TRPV channel gene as a target of environmental programming. OSM-9 is expressed in multiple sensory neurons and is essential for mechanosensory, osmosensory, and chemosensory behaviors. In control adults, gfp driven by ~350 bp of osm-9 upstream regulatory sequences was expressed in the ADL and AWA neurons, whereas gfp was only expressed in AWA neurons of postdauer adults. Analysis of the osm-9 upstream regulatory sequence yielded a cis-acting motif that is necessary for the downregulation of osm-9 in ADL, and is competitively bound by the negative regulator, DAF-3 SMAD, and unknown activators. In addition, we found that the ADL-mediated and osm-9 dependent ascr#3 avoidance behavior is significantly reduced in wildtype postdauer adults compared to controls, indicating that the endogenous osm-9 gene is downregulated similarly to the gfp reporter. Using the ascr#3 avoidance assay, we investigated the mechanism of osm-9 regulation by testing the behavior of control and postdauer animals in strains carrying mutations in dauer formation, RNAi, and chromatin remodeling genes. Our results indicated that the differential expression of osm-9 was mediated by TGF-β signaling and required functional chromatin remodeling pathways. Moreover, we found that the Mutator and ERGO-1 26G RNAi pathways are also required for the regulation of osm-9 expression. We showed that MUT-16 modulates the expression of daf-3, and is required in ADL neurons for the differential expression of osm-9. Together, our results suggest that RNAi pathways regulate osm-9 expression indirectly via modulation of TGF-β signaling, and that the altered expression pattern is maintained by the chromatin state at the osm-9 locus. Our results describe an elegant mechanism by which developmental experience influences adult phenotypes by establishing and maintaining transcriptional changes via RNAi and chromatin remodeling pathways.
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