Neurotrophin-3 signaling maintains maturational homeostasis between neuronal populations in the olfactory epithelium

Simpson, P. Jeanette; Wang, Eugene; Moon, Cheil; Matarazzo, Valéry; Cohen, Deborah R.S; Liebl, Daniel J.; Ronnett, Gabriele V.

doi:10.1016/j.mcn.2003.08.001

Cited by 42 publications

(25 citation statements)

References 53 publications

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“…This hints at the hypothesis that the MAPKs present in these regions are activated by alternative pathways [e.g., neurotrophins that also have been shown to activate MAPKs (Simpson et al, 2003)] not examined in our study. Another example is the absence of Braf from the dentate gyrus (DG) of the hippocampus, indicating that, even though BRAF is the most prominent RAF protein in the adult mammalian brain and the most effective kinase in phosphorylating MEK1 and MEK2, it may be possible that, in the DG, CRAF is responsible for the activation of downstream MEKs (Papin et al, 1996;Wellbrock et al, 2004).…”

Section: General Considerationssupporting

confidence: 63%

“…Notably, Mek1 expression is confined to the granule cell layer of the OB; Erk5 is restricted to the glomerular cell layer; and Erk1 and Erk2 are present in both of these regions, where new local circuit neurons are undergoing terminal differentiation throughout life. In support of the hypothesis that the MAPK signalling pathway plays a crucial role in neuronal differentiation process in the adult central nervous system, it has recently been shown that the activation of receptor kinases via neurotrophins upstream of MAPKs is necessary for maintenance of the homeostasis between precursor and mature neuronal populations (Simpson et al, 2003). Moreover, recent studies show that neurotrophins are good candidates for contributing to regenerative processes in the OB (Linnarsson et al, 2000; for review see Mackay-Sim and Chuah, 2000).…”

Section: Mapk Pathway and Neurogenesis In The Adult Brainmentioning

confidence: 98%

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Differential mRNA distribution of components of the ERK/MAPK signalling cascade in the adult mouse brain

Benedetto

Hitz

Hölter

et al. 2006

J of Comparative Neurology

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The mitogen-activated protein kinases (MAPKs), also called extracellular signal-regulated kinases (ERKs), are a group of serine/threonine terminal protein kinases activated downstream of a pleiotrophy of transmembrane receptors. Main intracellular components of the MAPK signalling pathway are the RAF, MEK, and ERK proteins, which work in a cascade of activator and effector proteins. They regulate many fundamental cellular functions, including cell proliferation, cell survival, and cell differentiation by transducing extracellular signals to cytoplasmic and nuclear effectors. To reveal more details about possible activation cascades in this pathway, the present study gives a complete description of the differential expression of Braf, Mek1, Mek2, Mek5, Erk1, Erk2, Erk3, and Erk5 in the adult murine brain by way of in situ hybridization analysis. In this study, we found that each gene is widely expressed in the whole brain, except for Mek2, but each displays a very distinct expression pattern, leading to distinct interactions of the MAPK components within different regions. Most notably we found that 1) Braf and Erk3 are coexpressed in the hippocampus proper, confirming a possible functional interaction; 2) in most forebrain areas, Mek5 and Erk5 are coexpressed; and 3) in the neurogenic regions of the brain, namely, the olfactory bulb and the dentate gyrus, Braf is absent, indicating that other activator proteins have to take over its function. Despite these differences, our results show widespread coexpression of the pathway components, thereby confirming the hypothesis of redundant functions among several MEK and ERK proteins in some regions of the brain.

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Section: General Considerationssupporting

confidence: 63%

Section: Mapk Pathway and Neurogenesis In The Adult Brainmentioning

confidence: 98%

Differential mRNA distribution of components of the ERK/MAPK signalling cascade in the adult mouse brain

Benedetto

Hitz

Hölter

et al. 2006

J of Comparative Neurology

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“…Interestingly, NT-3 was reported to reduce neuronal precursor proliferation and inhibit neuronal maturation. These effects of NT-3 maintain homeostasis between neuronal populations within the olfactory epithelium in mice (Simpson et al, 2003).…”

Section: Discussionmentioning

confidence: 96%

Prolonged exposure to NT-3 attenuates cholinergic nerve-mediated contractions in cultured murine airways

Bachar

Adner

Uddman

et al. 2005

Respiratory Physiology & Neurobiology

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Prolonged exposure to NT-3 attenuates cholinergic nerve-mediated contractions in cultured murine airways.Bachar, Ofir; Adner, Mikael; Uddman, Rolf; Cardell, Lars-Olaf General rights Copyright and moral rights for the publications made accessible in the public portal are retained by the authors and/or other copyright owners and it is a condition of accessing publications that users recognise and abide by the legal requirements associated with these rights.• Users may download and print one copy of any publication from the public portal for the purpose of private study or research.• You may not further distribute the material or use it for any profit-making activity or commercial gain • You may freely distribute the URL identifying the publication in the public portal AbstractChronic airway inflammation may induce subsequent airway hyperresponsiveness (AHR) including pathological alteration of neural activity. Asthmatic airways contain elevated levels of neurotrophin-3 (NT-3) and brain-derived neurotrophic factor (BDNF) albeit; their effect on neural activity is unclear. This study evaluates the effects of NT-3 and BDNF on nerve mediated airway contractions in-vitro. Tracheal segments from BALB/c mice were cultured for 4 days with NT-3 or BDNF. Responsiveness to electric field stimulation (EFS) was evaluated in organ-bath and innervation patterns were examined by quantitative immunohistochemistry. In cultured segments the EFS induced contractions were inhibited by tetrodotoxin or atropine. NT-3 reduced the EFS contractions in a concentration-dependent manner whereas BDNF had no effect. The amount of nerve fibers, found in conjunction with the tracheal smooth muscle, was similar in NT-3 treated and control segments. In conclusion, NT-3 attenuates cholinergic nerve-mediated contractions of airway in-vitro. Considering the elevated levels of NT-3 found in asthmatic airways, the findings imply a protective role of NT-3 in AHR.

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“…14 Sustentacular support cells provide many of the extrinsic factors that regulate the dynamics of the neuronal population. [15][16][17] Neurogenesis is hypothesized to begin with exposure of globose basal cells to external signals that direct them to undergo a single round of asymmetric division producing a progenitor cell that migrates apically out of basal cell layer. This progenitor undergoes symmetric rounds of division to produce immediate neuronal precursors (INPs), which go through multiple rounds of division to generate offspring that differentiate to become immature OSNs.…”

Section: Introductionmentioning

confidence: 99%

Progressive and Inhibitory Cell Cycle Proteins Act Simultaneously to Regulate Neurotrophin-mediated Proliferation and Maturation of Neuronal Precursors

Simpson

Moon²,

Kleman

et al. 2007

Cell Cycle

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ACKnowlEdGEMEntSWe thank Amy Palmer for helpful discussions and reading of the manuscript, and Susan McTeer for manuscript preparation. This work was supported by grants NIDCD RO3 DC005704 to P.J.S., NIDCD RO1 DC02979 and NINDS RO1 NS39657 to G.V.R. AbStRACtNeuronal stem cell expansion and differentiation is a process involving stages of proliferation and maturation governed by the sequential and combinatorial exposure of cells to extrinsic factors. The olfactory epithelium is an excellent model to investigate regulation of this process, as it undergoes neuronal replacement post-natally. We have shown that the neurotrophins NGF and BDNF sequentially promote proliferation of developing olfactory sensory neuronal precursors, although their kinetics of proliferation and cell fate outcomes differ. Interestingly, CNP inhibits this neurotrophin-induced proliferation and promotes the maturation of these precursors to their next developmental stage. Here, we investigate the mechanisms behind these actions. Both NGF and BDNF increase the expression of cyclin D1 and cyclin-dependent kinase 4 (cdk4), with temporal expression patterns that parallel the proliferation kinetics of their cellular targets. The timing of cyclin D1 expression reflects differences in the need for transcription and translation in early and late stage precursors. CNP inhibits neurotrophin-induced cyclin D1 expression, and induces the expression of different profiles of inhibitory cell cycle proteins, which are neurotrophin-specific and correlate with the attainment of different maturational cell fates. Inhibition of protein degradation reverses the effects of neurotrophins and CNP on cyclin D1 and inhibitor expression levels, respectively. These results suggest a model for cell cycle regulation that involves the simultaneous expression of progressive and inhibitory cell cycle regulatory proteins in response to both proliferation and differentiation agents, followed by selective degradation of these proteins, providing a mechanism for rapid and exquisite control of the cell cycle.

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Neurotrophin-3 signaling maintains maturational homeostasis between neuronal populations in the olfactory epithelium

Cited by 42 publications

References 53 publications

Differential mRNA distribution of components of the ERK/MAPK signalling cascade in the adult mouse brain

Differential mRNA distribution of components of the ERK/MAPK signalling cascade in the adult mouse brain

Prolonged exposure to NT-3 attenuates cholinergic nerve-mediated contractions in cultured murine airways

Progressive and Inhibitory Cell Cycle Proteins Act Simultaneously to Regulate Neurotrophin-mediated Proliferation and Maturation of Neuronal Precursors

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