Gene regulatory mechanisms underlying evolutionary adaptations of homologous neuronal cell types

Abstract

How nervous systems coordinate the generation of specific neuron types with gene expression plasticity and how these mechanisms impact cell type evolution is unknown. Here we use Caenorhabditis species to study neuron-type robustness, plasticity and evolution, using VC4 and VC5 cholinergic motoneurons as models. In C. elegans, we found that epigenetic silencing through histone 3 lysine 9 methylation (H3K9me) is necessary to suppress the expression of the serotonin reuptake gene mod-5/Sert and a serotonergic phenotype in these cells. In contrast, we observed that VC4 and VC5 neurons in the Angaria group of species of the Caenorhabditis genus have evolved an intense serotonergic staining. This phenotype is caused by the emergence of a new enhancer in the mod-5/Sert locus, which has been recruited to the ancestral neuron-type gene regulatory network. Enhancer transfer from C. angaria is sufficient to impose a constitutive serotonergic fate in C. elegans. Remarkably, acquiring this new trait modulates egg-laying responses to high levels of exogenous serotonin, which can be found in specific environments. Finally, we discovered that the repression of the serotonergic fate in C. elegans VC4 and VC5 neurons is indeed a plastic trait that can be adjusted in specific environmental growth conditions to elicit egg-laying behaviours similar to those observed in Angaria species. Our work identifies gene regulatory mechanisms that coordinate the generation of robust neuron-type-specific programs with plastic gene expression responses. These findings identify a gene regulatory framework underlying the evolution of neuron-type-specific features and the emergence of novel behaviours.