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In vertebrates, the embryonic olfactory epithelium contains progenitors that will give rise to distinct classes of neurons, including olfactory sensory neurons (OSN, involved in odor detection), vomeronasal sensory neurons (VSN, responsible for pheromone sensing) and GnRH neurons that control the hypothalamic-pituitary-gonadal axis. Currently, these three neuronal lineages are usually believed to emerge from uniform pools of progenitors. Here we found that the homeodomain transcription factor Dbx1 is expressed by neurogenic progenitors in the developing and adult mouse olfactory epithelium. We demonstrate that Dbx1 itself is dispensable for neuronal fate specification and global organization of the olfactory sensory system. Using lineage tracing we characterize the contribution of Dbx1 lineages to OSN, VSN and GnRH neuron populations and reveal an unexpected degree of diversity. Furthermore, we demonstrate thatDbx1-expressing progenitors remain neurogenic in the absence of the proneural geneAscl1. Our work therefore points to the existence of distinct neurogenic programs in Dbx1-derived and other olfactory lineages.

Background: The ability to manipulate the activity of interneurons with optogenetic tools offers the possibility of interfering with diseases caused by altered neuronal inhibition and synchrony, including epilepsy and schizophrenia. To develop vectors for therapeutic approaches, targeting optogenetic constructs to interneurons is therefore a key requirement. We investigated whether the interneuron‐specific promoters glutamic acid decarboxylase (GAD)67 and cholecystokinin (CCK) allowed targeted lentiviral delivery of opsins to interneurons as a whole, or specifically CCK+ interneurons. Methods: We generated lentiviral (LV) plasmids encoding channelrhodopsin (ChR2) and halorhodopsin (NpHR) tagged with fluorophores and driven by GAD67 or CCK promoters. Adeno‐associated virus (AAV) and LV vectors carrying opsins driven by pyramidal cell promoters were used as controls. We transduced neuronal cultures and rodent brain in vivo, immunostained specimens 6–8 weeks after in vivo injection and 7–14 days after in vitro transduction, and evaluated volume and specificity of expression by confocal microscopy. Results: In vitro, 90% (19/21) of LV‐CCK‐NpHR2.0‐EYFP expressing neurons were CCK+. In vivo, LV‐GAD67‐ChR2‐mCherry was expressed in 2.6% (5/193), LV‐GAD67‐NpHR2.0‐EYFP in approximately 15% (43/279) and LV‐CCK‐NpHR2.0‐EYFP in 47% (9/19) of hippocampal GABA+ interneurons. GAD67 vectors expressed in larger volumes than CCK‐driven constructs. AAV vector controls achieved the largest expression volumes. Conclusions: LV‐CCK‐NpHR2.0‐EYFP may be useful for targeting CCK+ interneurons in culture. GAD67/CCK‐driven lentiviral constructs are expressed in vivo, although expression is not specific for interneurons. Overall, expression levels are low compared to opsins driven by pyramidal cell promoters. A better understanding of GAD67 and CCK promoter structure or alternative techniques is required to reliably target opsins to interneurons using viral vectors.

J. Neurochem. (2011) 116, 606–615. Abstract Calcium is a universal signal, and its capacity to encode intracellular messages via spatial, temporal and amplitude characteristics allows it to participate in most cellular events. In a specific context, calcium plays a pivotal role in migration, although its role has not been elucidated fully. By using immortalized gonadotropin-releasing hormone-secreting neurons (GN11), we have now investigated the role of TRPV4, a member of the vanilloid family of Ca2+ channels, in neuronal migration. Our results show that TRPV4 channels are present and functional in GN11 cells and their localization is polarized and enriched in lamellipodial structures. TRPV4 activation leads to a retraction of the lamellipodia and to a decrease in migratory behaviour; moreover cells migrate slower and in a more random manner. We therefore provide evidence for a new regulation of gonadotropin-releasing hormone neurons and a new role for calcium at the leading edge of migratory cells.