Sequential Arrival and Graded Secretion of Sema3F by Olfactory Neuron Axons Specify Map Topography at the Bulb

Takeuchi, Haruki; Inokuchi, Kasumi; Aoki, Mari; Suto, Fumikazu; Tsuboi, Akito; Matsuda, Ikuo; Suzuki, Misao; Aiba, Atsu; Serizawa, Shou; Yoshihara, Yoshihiro; Fujisawa, Hajime; Sakano, Hitoshi

doi:10.1016/j.cell.2010.04.041

Cited by 124 publications

(206 citation statements)

References 60 publications

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“…For these experiments, we used mice in which the #123 promoter drives Cre recombinase in olfactory sensory neurons but not in the resident cells of the olfactory bulb (16)(17)(18). The specificity of this driver was confirmed by crossing mice expressing #123-Cre with a strain harbouring the tdTomato reporter (R26 loxP-STOP-loxPtdTomato ) (19).…”

Section: Quantification Of Fragile X Granule Componentsmentioning

confidence: 99%

“…Mice harbouring either a Cre-sensitive Rosa26 tdTomato reporter allele (Jackson Laboratory; Bar Harbor, ME) (19) or a Cresensitive Fmr1 allele (20) were crossed to mice in which Cre expression is driven by the Synapsin 1 promoter (Jackson Laboratory) or to mice in which Cre expression is driven specifically in olfactory sensory neurons by the #123 promoter (16)(17)(18). Previous characterization of the Synapsin Cre mouse line indicates that, rather than the expected pan-neuronal expression, this transgene drives Cre expression in populations of neurons including dentate and CA3 pyramidal neurons in hippocampus, neurons in thalamic relay nuclei, and a subpopulation of layer IV neurons in neocortex (21,14).…”

Section: Quantification Of Fxg Identificationmentioning

confidence: 99%

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Axonal ribosomes and mRNAs associate with fragile X granules in adult rodent and human brains

et al. 2017

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Local mRNA translation in growing axons allows for rapid and precise regulation of protein expression in response to extrinsic stimuli. However, the role of local translation in mature CNS axons is unknown. Such a mechanism requires the presence of translational machinery and associated mRNAs in circuit-integrated brain axons. Here we use a combination of genetic, quantitative imaging and super-resolution microscopy approaches to show that mature axons in the mammalian brain contain ribosomes, the translational regulator FMRP and a subset of FMRP mRNA targets. This axonal translational machinery is associated with Fragile X granules (FXGs), which are restricted to axons in a stereotyped subset of brain circuits. FXGs and associated axonal translational machinery are present in hippocampus in humans as old as 57 years. This FXGassociated axonal translational machinery is present in adult rats, even when adult neurogenesis is blocked. In contrast, in mouse this machinery is only observed in juvenile hippocampal axons. This differential developmental expression was specific to the hippocampus, as both mice and rats exhibit FXGs in mature axons in the adult olfactory system. Experiments in Fmr1 null mice show that FMRP regulates axonal protein expression but is not required for axonal transport of ribosomes or its target mRNAs. Axonal translational machinery is thus a feature of adult CNS neurons. Regulation of this machinery by FMRP could support complex behaviours in humans throughout life.

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Section: Quantification Of Fragile X Granule Componentsmentioning

confidence: 99%

Section: Quantification Of Fxg Identificationmentioning

confidence: 99%

Axonal ribosomes and mRNAs associate with fragile X granules in adult rodent and human brains

et al. 2017

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“…Two levels of guidance have been identified. The first directs axons to their target zones in the bulb and the second guides local axon sorting, which ends in glomerular segregation Imai et al, 2006Imai et al, , 2009Nakashima et al, 2013;Nishizumi and Sakano, 2015;Rodriguez-Gil et al, 2015;Serizawa et al, 2006;Takeuchi et al, 2010;Wang et al, 1998). The current model explaining global targeting (at least on the medial side of the bulb) proposes the existence of guidance cues that determine the position of the target along two axes in the bulb: one dorsoventral and the other anteroposterior.…”

Section: Introductionmentioning

confidence: 99%

Alteration of Nrp1 signaling at different stages of olfactory neuron maturation promotes glomerular shifts along distinct axes in the olfactory bulb

et al. 2016

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Building the topographic map in the mammalian olfactory bulb is explained by a model based on two axes along which sensory neurons are guided: one dorsoventral and one anteroposterior. This latter axis relies on specific expression levels of Nrp1. To evaluate the role of this receptor in this process, we used an in vivo genetic approach to decrease or suppress Nrp1 in specific neuronal populations and at different time points during axonal targeting. We observed, in neurons that express the M71 or M72 odorant receptors, that Nrp1 inactivation leads to two distinct wiring alterations, depending on the time at which Nrp1 expression is altered: first, a surprising dorsal shift of the M71 and M72 glomeruli, which 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 Sema3A and in mice whose sensory neurons express an Nrp1 mutant unable to bind Sema3A. 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 elsewhere. Together, these findings show drastically different axonal targeting outcomes dependent on the timing at which Nrp1/ Sema3A signaling is altered.

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“…The reason why there is no obvious defect in peripheral branch in the Ntf3 cKO mice might be attributed to the presence of many repulsive cues around the DRG (Keynes et al, 1997;Masuda et al, 2008); that is, sensory axons may finally find their route and fasciculate with motoneuron axons without attractive cues. After fasciculation, it is possible that Ntf3 is secreted from motor axons as a transaxonal signaling factor, analogous to the secretion of Sema3a and Sema3f from developing axons (Moret et al, 2007;Takeuchi et al, 2010). At E15, central branches of sensory neurons enter spinal cord from the dorsal root entry zone after the waiting period (Ozaki and Snider, 1997;Watanabe et al, 2006), and, then, proprioceptive axons directly innervate motoneurons.…”

Section: Role Of Motoneuron-derived Ntf3 On Spinal Circuit Formationmentioning

confidence: 99%

“…For example, Sema3e and its high-affinity receptor plexin D1 (Plxnd1), which are expressed by selected motoneuron pools and proprioceptive sensory neurons, respectively, are crucial determinants of synaptic specificity in sensory-motor circuits (Pecho-Vrieseling et al, 2009). It is known that early-born neurons regulate late-born neurons during development of some neuronal circuits, such as the olfactory pathway (Takeuchi et al, 2010) and the thalamocortical pathway (McConnell et al, 1989). As motoneuron development precedes sensory neuron development (Wentworth, 1984;Landmesser and Honig, 1986;Wang et al, 2011), it is conceivable that motoneurons have substantial roles in sensory neuron development.…”

Section: Introductionmentioning

confidence: 99%

Role of motoneuron-derived neurotrophin 3 in survival and axonal projection of sensory neurons during neural circuit formation

et al. 2012

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SUMMARYSensory neurons possess the central and peripheral branches and they form unique spinal neural circuits with motoneurons during development. Peripheral branches of sensory axons fasciculate with the motor axons that extend toward the peripheral muscles from the central nervous system (CNS), whereas the central branches of proprioceptive sensory neurons directly innervate motoneurons. Although anatomically well documented, the molecular mechanism underlying sensory-motor interaction during neural circuit formation is not fully understood. To investigate the role of motoneuron on sensory neuron development, we analyzed sensory neuron phenotypes in the dorsal root ganglia (DRG) of Olig2 knockout (KO) mouse embryos, which lack motoneurons. We found an increased number of apoptotic cells in the DRG of Olig2 KO embryos at embryonic day (E) 10.5. Furthermore, abnormal axonal projections of sensory neurons were observed in both the peripheral branches at E10.5 and central branches at E15.5. To understand the motoneuron-derived factor that regulates sensory neuron development, we focused on neurotrophin 3 (Ntf3; NT-3), because Ntf3 and its receptors (Trk) are strongly expressed in motoneurons and sensory neurons, respectively. The significance of motoneuron-derived Ntf3 was analyzed using Ntf3 conditional knockout (cKO) embryos, in which we observed increased apoptosis and abnormal projection of the central branch innervating motoneuron, the phenotypes being apparently comparable with that of Olig2 KO embryos. Taken together, we show that the motoneuron is a functional source of Ntf3 and motoneuron-derived Ntf3 is an essential pre-target neurotrophin for survival and axonal projection of sensory neurons.

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Sequential Arrival and Graded Secretion of Sema3F by Olfactory Neuron Axons Specify Map Topography at the Bulb

Cited by 124 publications

References 60 publications

Axonal ribosomes and mRNAs associate with fragile X granules in adult rodent and human brains

Axonal ribosomes and mRNAs associate with fragile X granules in adult rodent and human brains

Alteration of Nrp1 signaling at different stages of olfactory neuron maturation promotes glomerular shifts along distinct axes in the olfactory bulb

Role of motoneuron-derived neurotrophin 3 in survival and axonal projection of sensory neurons during neural circuit formation

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