Polarized Signaling Endosomes Coordinate BDNF-Induced Chemotaxis of Cerebellar Precursors

Zhou, Pengcheng; Porcionatto, Marimélia; Pilapil, Mariecel; Chen, Yi-Cheng; Choi, Yoojin; Tolias, Kimberley F.; Bikoff, Jay B.; Hong, Elizabeth J.; Greenberg, Michael E.; Segal, Rosalind A.

doi:10.1016/j.neuron.2007.05.030

Cited by 147 publications

(167 citation statements)

References 123 publications

(122 reference statements)

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“…To determine if a similar mechanism occurs in dendrites, we first asked if endocytosis is required for BDNF-mediated dendriteto-nucleus signaling. Previous findings demonstrated that the GTPase dynamin is required for TrkB receptor internalization (31). To assess the requirement of dynamin-mediated endocytosis for dendritic BDNF-induced IEG expression, we used the selective dynamin inhibitor dynasore (32).…”

Section: Intracellular Calcium Is Differentially Required For Dendritmentioning

confidence: 99%

Neurotrophin-mediated dendrite-to-nucleus signaling revealed by microfluidic compartmentalization of dendrites

Cohen

Bas‐Orth

Kim

et al. 2011

Proc. Natl. Acad. Sci. U.S.A.

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Signaling from dendritic synapses to the nucleus regulates important aspects of neuronal function, including synaptic plasticity. The neurotrophin brain-derived neurotrophic factor (BDNF) can induce long-lasting strengthening of synapses in vivo and this effect is dependent on transcription. However, the mechanism of signaling to the nucleus is not well understood. Here we describe a microfluidic culture device to investigate dendrite-to-nucleus signaling. Using these microfluidic devices, we demonstrate that BDNF can act directly on dendrites to elicit an anterograde signal that induces transcription of the immediate early genes, Arc and c-Fos. Induction of Arc is dependent on dendrite-and cell body-derived calcium, whereas induction of c-Fos is calcium-independent. In contrast to retrograde neurotrophin-mediated axon-to-nucleus signaling, which is MEK5-dependent, BDNF-mediated anterograde dendrite-to-nucleus signaling is dependent on MEK1/2. Intriguingly, the activity of TrkB, the BDNF receptor, is required in the cell body for the induction of Arc and c-Fos mediated by dendritically applied BDNF. These results are consistent with the involvement of a signaling endosome-like pathway that conveys BDNF signals from the dendrite to the nucleus.gene expression | mRNA translation

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Section: Intracellular Calcium Is Differentially Required For Dendritmentioning

confidence: 99%

Neurotrophin-mediated dendrite-to-nucleus signaling revealed by microfluidic compartmentalization of dendrites

Cohen

Bas‐Orth

Kim

et al. 2011

Proc. Natl. Acad. Sci. U.S.A.

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“…These include cell polarity, cell motility, and chemotaxis, as well as neuronal migration and polarization; however, these observations are drawn almost exclusively from the use of pharmacological inhibitors such as Wortmanin or LY294002 (Polleux et al 2002;Shi et al 2003;Jossin and Goffinet 2007;Zhou et al 2007). The best characterized class Ia PI3-kinase (PI3KcIa) is involved in the formation of phosphatidylinositol (3,4,5)-triphosphate (PIP3), and it lies downstream of Ras and upstream of protein kinase B (or AKT) during signal transduction.…”

Section: Pi3-kinase Signaling and Axon Specificationmentioning

confidence: 99%

Initiating and Growing an Axon

Polleux¹,

Snider²

2010

Cold Spring Harbor Perspectives in Biology

155

127

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The ability of neurons to form a single axon and multiple dendrites underlies the directional flow of information transfer in the central nervous system. Dendrites and axons are molecularly and functionally distinct domains. Dendrites integrate synaptic inputs, triggering the generation of action potentials at the level of the soma. Action potentials then propagate along the axon, which makes presynaptic contacts onto target cells. This article reviews what is known about the cellular and molecular mechanisms underlying the ability of neurons to initiate and extend a single axon during development. Remarkably, neurons can polarize to form a single axon, multiple dendrites, and later establish functional synaptic contacts in reductionist in vitro conditions. This approach became, and remains, the dominant model to study axon initiation and growth and has yielded the identification of many molecules that regulate axon formation in vitro (Dotti et al. 1988). At present, only a few of the genes identified using in vitro approaches have been shown to be required for axon initiation and outgrowth in vivo. In vitro, axon initiation and elongation are largely intrinsic properties of neurons that are established in the absence of relevant extracellular cues. However, the importance of extracellular cues to axon initiation and outgrowth in vivo is emerging as a major theme in neural development (Barnes and Polleux 2009). In this article, we focus our attention on the extracellular cues and signaling pathways required in vivo for axon initiation and axon extension.

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“…As previous reports of BDNF-mediated cerebellar development suggest that BDNF-mediated cellular migration is dependent on a standing gradient of BDNF (Zhou et al, 2007), we investigated the distribution of BDNF protein along the rostrocaudal axis of the OB via ELISA. We found that BDNF protein levels were significantly lower in the OB than in the hippocampus (t test, t (8) ϭ 6.680, p Ͻ 0.001).…”

Section: Altered Bdnf-trkb Signaling Leads To Regional Alterations Inmentioning

confidence: 99%

Variant Brain-Derived Neurotrophic Factor (Val66Met) Alters Adult Olfactory Bulb Neurogenesis and Spontaneous Olfactory Discrimination

Bath¹,

Mandairon²,

Jing³

et al. 2008

J. Neurosci.

144

173

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Neurogenesis, the division, migration, and differentiation of new neurons, occurs throughout life. Brain derived neurotrophic factor (BDNF) has been identified as a potential signaling molecule regulating neurogenesis in the subventricular zone (SVZ), but its functional consequences in vivo have not been well defined. We report marked and unexpected deficits in survival but not proliferation of newly born cells of adult knock-in mice containing a variant form of BDNF [a valine (Val) to methionine (Met) substitution at position 66 in the prodomain of BDNF (Val66Met)], a genetic mutation shown to lead to a selective impairment in activity-dependent BDNF secretion. Utilizing knock-out mouse lines, we identified BDNF and tyrosine receptor kinase B (TrkB) as the critical molecules for the observed impairments in neurogenesis, with p75 knock-out mice showing no effect on cell proliferation or survival. We then localized the activated form of TrkB to a discrete population of cells, type A migrating neuroblasts, and demonstrate a decrease in TrkB phosphorylation in the SVZ of Val66Met mutant mice. With these findings, we identify TrkB signaling, potentially through activity dependent release of BDNF, as a critical step in the survival of migrating neuroblasts. Utilizing a behavioral task shown to be sensitive to disruptions in olfactory bulb neurogenesis, we identified specific impairments in spontaneous olfactory discrimination, but not general olfactory sensitivity or habituation to olfactory stimuli in BDNF mutant mice. Through these observations, we have identified novel links between genetic variant BDNF and adult neurogenesis in vivo, which may contribute to significant impairments in olfactory function.

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Polarized Signaling Endosomes Coordinate BDNF-Induced Chemotaxis of Cerebellar Precursors

Cited by 147 publications

References 123 publications

Neurotrophin-mediated dendrite-to-nucleus signaling revealed by microfluidic compartmentalization of dendrites

Neurotrophin-mediated dendrite-to-nucleus signaling revealed by microfluidic compartmentalization of dendrites

Initiating and Growing an Axon

Variant Brain-Derived Neurotrophic Factor (Val66Met) Alters Adult Olfactory Bulb Neurogenesis and Spontaneous Olfactory Discrimination

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