staff

Julien Dal Col

Senior Research Associate in Neurogenetics

  • T: +41 22 379 33 39
  • office 4031a (Sciences III)

  • A toolbox for genetic targeting of the claustrum bioRxiv 2024.05.13.593837; doi: https://doi.org/10.1101/2024.05.13.593837

    abstract

    The claustrum (CLA), a subcortical nucleus in mammals, essentially composed of excitatory projection neurons and known for its extensive connections with the neocortex, has recently been associated with a variety of functions ranging from consciousness to impulse control. However, research on the CLA has been challenging due to difficulties in specifically and comprehensively targeting its neuronal populations. In various cases, this limitation has led to inconsistent findings and a lack of reliable data. In the present work, we describe the expression profile of the Smim32 gene, which is almost exclusively transcribed in excitatory neurons of the CLA and the endopiriform nucleus, as well as in inhibitory neurons of the thalamic reticular nucleus. Leveraging this unique expression pattern, we developed a series of Cre- and Flippase-expressing knockin and BAC transgenic mouse lines with different expression profiles. With these novel tools in hand, we propose new standards for the interrogation of CLA function.

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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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  • 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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  • Adenylyl cyclase-dependent axonal targeting in the olfactory system. Development 2007 Jul;134(13):2481-9. dev.006346. 10.1242/dev.006346.

    abstract

    The vertebrate olfactory bulb is a remarkably organized neuronal structure, in which hundreds of functionally different sensory inputs are organized into a highly stereotyped topographical map. How this wiring is achieved is not yet understood. Here, we show that the olfactory bulb topographical map is modified in adenylyl cyclase 3 (adenylate cyclase 3)-deficient mice. In these mutants, axonal projection targets corresponding to specific odorant receptors are disorganized, are no longer exclusively innervated by functionally identical axonal projections and shift dramatically along the anteroposterior axis of the olfactory bulb. Moreover, the cyclase depletion leads to the prevention of neuropilin 1 (Nrp1) expression in olfactory sensory neuron axonal projections. Taken together, our data point to a major role played by a crucial element of the odorant-induced transduction cascade, adenylyl cyclase 3, in the targeting of olfactory sensory neuron axons towards the brain. This mechanism probably involves the regulation of receptor genes known to be crucial in axonal guidance processes.

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