staff

Quentin Dietschi

Postdoctoral fellow in Neurogenetics

  • T: +41 22 379 34 18
  • office 4037a (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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  • Alteration of Nrp1 signaling at different stages of olfactory neuron maturation promotes glomerular shifts along distinct axes in the olfactory bulb. Development 2016 Aug;():. dev.138941. 10.1242/dev.138941.

    abstract

    The building of the topographic map in the mammalian olfactory bulb is explained by a model based on two axes along which sensory neurons are guided: one dorso-ventral and the other antero-posterior. This latter axis relies on specific expression levels of Neuropilin 1 (Nrp1). To evaluate the role played by this receptor in this process, we used an in vivo genetic approach to decrease or suppress it in specific neuronal populations and at different time points during axonal targeting. We observed, in neurons that express either the M71 or the M72 odorant receptors, that the inactivation of Nrp1 leads to two distinct wiring alterations, whose incidence depends on the time at which Nrp1 expression is altered: first, a surprising dorsal shift of the M71 and M72 glomeruli that often fuse with their contralateral counterparts, and second, the formation of anteriorized glomeruli. The two phenotypes are partly recapitulated in mice lacking the Nrp1 ligand Semaphorin 3A (Sema3A), and in mice whose sensory neurons express a Nrp1 mutant unable to bind Sema3A. Finally, by using a mosaic conditional approach, we show that M71 axonal fibers can bypass the Nrp1 signals that define their target area, since they are hijacked and coalesce with Nrp1-deficient M71-expressing axons that target somewhere else. Together, these findings show drastically different axonal targeting outcomes dependent on the timing at which Nrp1/Sema3A signaling is altered.

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  • Convergence of FPR-rs3-expressing neurons in the mouse accessory olfactory bulb. Mol. Cell. Neurosci. 2013 Sep;56():140-7. S1044-7431(13)00056-0. 10.1016/j.mcn.2013.04.008.

    abstract

    In the mouse, most members of the FPR receptor family are expressed by vomeronasal sensory neurons. The neural circuitry corresponding to this class of chemical sensors is unknown. Taking advantage of the presence of FPR-rs3 on both vomeronasal dendrites and axonal fibers, we visualized the distribution of sensory cells expressing this member of the FPR family, and their corresponding axonal projections in the olfactory bulb. We found a rostrocaudal gradient of receptor choice frequency in the vomeronasal sensory neuroepithelium, and observed a convergence of FPR-rs3 axons into multiple, linked and deeply located glomeruli. These were homogenously innervated, and spatially restricted to the basal portion of the rostral accessory olfactory bulb. This organization, reminiscent of the one that characterizes axonal projections of V1R-expressing neurons, supports a role played by these receptors in the perception of semiochemicals.

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