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Mora-Martinez, C.

Publications and source records attributed to Mora-Martinez, C..

2 recordsLinked to original sources

Gene regulatory mechanisms underlying evolutionary adaptations of homologous neuronal cell types

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.

evolutionary biology↗

Forkhead transcription factor FKH-8 is a master regulator of primary cilia in C. elegans

Cilia, either motile or non-motile (a.k.a primary or sensory), are complex evolutionary conserved eukaryotic structures composed of hundreds of proteins required for their assembly, structure and function that are collectively known as the ciliome. Ciliome mutations underlie a group of pleiotropic genetic diseases known as ciliopathies. Proper cilium function requires the tight coregulation of ciliome gene transcription, which is only fragmentarily understood. RFX transcription factors (TF) have an evolutionarily conserved role in the direct activation of ciliome genes both in motile and non-motile cilia cell types. In vertebrates, FoxJ1 and FoxN4 Forkhead (FKH) TFs work with RFX in the direct activation of ciliome genes, exclusively in motile cilia cell-types. No additional TFs have been described to act together with RFX in primary cilia cell-types in any organism. Here we describe FKH-8, a FKH TF, as master regulator of the primary ciliome in Caenorhabditis elegans. fkh-8 is expressed in all ciliated neurons in C. elegans, binds the regulatory regions of ciliome genes, regulates ciliome gene expression, cilium morphology and a wide range of behaviours mediated by sensory cilia. Importantly, we find FKH-8 function can be replaced by mouse FOXJ1 and FOXN4 but not by members of other mouse FKH subfamilies. In conclusion, our results show that RFX and FKH TF families act as master regulators of ciliogenesis also in sensory ciliated cell types and suggest that this regulatory logic could be an ancient trait predating functional cilia sub-specialization.

developmental biology↗