staff

Joël Tuberosa

PhD Student in Neurogenetics

  • T: +41 22 379 32 81
  • office 4031a (Sciences III)
  • Evolution of immune chemoreceptors into sensors of the outside world. Proc. Natl. Acad. Sci. U.S.A. 2017 Jun;():. 1704009114. 10.1073/pnas.1704009114.

    abstract

    Changes in gene expression patterns represent an essential source of evolutionary innovation. A striking case of neofunctionalization is the acquisition of neuronal specificity by immune formyl peptide receptors (Fprs). In mammals, Fprs are expressed by immune cells, where they detect pathogenic and inflammatory chemical cues. In rodents, these receptors are also expressed by sensory neurons of the vomeronasal organ, an olfactory structure mediating innate avoidance behaviors. Here we show that two gene shuffling events led to two independent acquisitions of neuronal specificity by Fprs. The first event targeted the promoter of a V1R receptor gene. This was followed some 30 million years later by a second genomic accident targeting the promoter of a V2R gene. Finally, we show that expression of a vomeronasal Fpr can reverse back to the immune system under inflammatory conditions via the production of an intergenic transcript linking neuronal and immune Fpr genes. Thus, three hijackings of regulatory elements are sufficient to explain all aspects of the complex expression patterns acquired by a receptor family that switched from sensing pathogens inside the organism to sensing the outside world through the nose.

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  • Large-scale transcriptional profiling of chemosensory neurons identifies receptor-ligand pairs in vivo. Nat. Neurosci. 2015 Oct;18(10):1455-63. nn.4100. 10.1038/nn.4100.

    abstract

    In mammals, olfactory perception is based on the combinatorial activation of G protein-coupled receptors. Identifying the full repertoire of receptors activated by a given odorant in vivo, a quest that has been hampered for over 20 years by technical difficulties, would represent an important step in deciphering the rules governing chemoperception. We found that odorants induced a fast and reversible concentration-dependent decrease in the transcription of genes corresponding to activated receptors in intact mice. On the basis of this finding, we developed a large-scale transcriptomic approach to uncover receptor-ligand pairs in vivo. We identified the mouse and rat odorant receptor signatures corresponding to specific odorants. Finally, we found that this approach, which can be used for species for which no genomic sequence is available, is also applicable to non-vertebrate species such as Drosophila.

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