Neuronal fate determinants of adult olfactory bulb neurogenesis

Abstract

Adult neurogenesis in mammals is restricted to two small regions, including the olfactory bulb, where GABAergic and dopaminergic interneurons are newly generated throughout the entire lifespan. However, the mechanisms directing them towards a specific neuronal phenotype are not yet understood. Here, we demonstrate the dual role of the transcription factor Pax6 in generating neuronal progenitors and also in directing them towards a dopaminergic periglomerular phenotype in adult mice. We present further evidence that dopaminergic periglomerular neurons originate in a distinct niche, the rostral migratory stream, and are fewer derived from precursors in the zone lining the ventricle. This regionalization of the adult precursor cells is further supported by the restricted expression of the transcription factor Olig2, which specifies transit-amplifying precursor fate and opposes the neurogenic role of Pax6. Together, these data explain both extrinsic and intrinsic mechanisms controlling neuronal identity in adult neurogenesis.

Spatio-temporal specification of olfactory bulb interneurons

“…Moreover, a recent work suggested a new concept of spatial separation of granule and periglomerular neurons specification. Retroviral lineage tracing showed that SVZ precursors generate few PG cells and more Gcs, whereas RMS precursors give rise to a larger population of PG neurons suggesting that in adult neurogenesis different neuronal subtypes are specified at different positions (Hack et al 2005 ). This regionalization appears to be at least partially mediated by Pax6 expression.…”

“…This regionalization appears to be at least partially mediated by Pax6 expression. Indeed, Pax6 expression in RMS precursor cells is required to progress towards a PG neuron subtype and its target deletion strongly reduces the proportion of PG cells normally generated (Hack et al 2005 ). Moreover, Pax6 governs the specific differentiation of dopaminergic periglomerular and superficial granule cells in the adultOB (Hack et al 2005 ;Kohwi et al 2005 ).…”

“…Indeed, Pax6 expression in RMS precursor cells is required to progress towards a PG neuron subtype and its target deletion strongly reduces the proportion of PG cells normally generated (Hack et al 2005 ). Moreover, Pax6 governs the specific differentiation of dopaminergic periglomerular and superficial granule cells in the adultOB (Hack et al 2005 ;Kohwi et al 2005 ). Pax6 is expressed in most proliferating SVZ progenitors but only in a subpopulation of migrating neuroblasts, further indicating that migrating neuroblasts are heterogeneous.…”

“…Transplantation of GFP-positive dLGE precursors from Pax6 knock-out mice into wild-type adult SVZ environment produce neuroblasts capable of migrating into the OB but fail to generate dopaminergic periglomerular and superficial granule cells (Kohwi et al 2005 ). Moreover, Pax6 overexpression in both SVZ and RMS is sufficient to induce differentiation of PG cells toward dopaminergic phenotypes (Hack et al 2005 ). According to the Hack study (2005 ), adult SVZ precursors proceed from a lesscommitted neurogenic state into the SVZ to a more-committed state closer to the OB, with many PG neurons precursors become fate-restricted at much more rostral position than granule neuron precursors.…”

Une altération de la neurogenèse conduit à des troubles de l’olfaction dans la sclérose en plaques

“…Alors que la genèse des neurones du bulbe olfactif constitue la fonction primordiale de la ZSV dans le cerveau adulte, des études de traçage cellulaire démontrent que les cellules B sont aussi à l'origine d'une population d'oligodendrocytes dans la substance blanche périventriculaire. La balance entre neurogenèse et oligodendrogenèse dans le cerveau post-natal et adulte serait gouvernée par l'interaction de déterminants neurogéniques tels que les facteurs Dlx2 (distal-less homeobox 2), Pax6 (paired box protein 6), et Olig2 (oligodendrocyte lineage transcription factor) qui régulent la genèse des oligodendrocytes, et dans certains cas, celle des astrocytes [7,8].…”