Conditional Knock-Out of β-<i>Catenin</i>in Postnatal-Born Dentate Gyrus Granule Neurons Results in Dendritic Malformation

Gao, Xiang; Arlotta, Paola; Macklis, Jeffrey D.; Chen, Jinhui

doi:10.1523/jneurosci.3206-07.2007

Cited by 93 publications

(86 citation statements)

References 45 publications

(47 reference statements)

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“…We also show that activation of Wnt/␤-catenin signaling leads to T-type current increase in thalamic cells. Previous studies on ␤-catenin in the adult brain have mainly focused on the role of the protein in dendritogenesis and synaptic function as a component of the cadherin adhesion complex (Yu and Malenka, 2003;Gao et al, 2007;Arikkath and Reichardt, 2008;Peng et al, 2009). The results presented here indicate the involvement of ␤-catenin in neuronal excitability not only by a local action at the synapse but also by regulating gene expression in thalamic neurons.…”

Section: Discussionmentioning

confidence: 99%

“…In the developing and adult brain, ␤-catenin is involved in neurogenesis (Chenn and Walsh, 2002;Zechner et al, 2003;Hirabayashi et al, 2004;Lie et al, 2005;Ivaniutsin et al, 2009;Kuwabara et al, 2009). In postmitotic neurons, membranous ␤-catenin, together with cadherins, participates in dendritogenesis (Yu and Malenka, 2003;Gao et al, 2007;Peng et al, 2009), synaptogenesis, and synaptic function (Arikkath and Reichardt, 2008). Recently, nuclear accumulation of ␤-catenin has been described in stimulated hippocampal cells (Chen et al, 2006;Abe and Takeichi, 2007;Schmeisser et al, 2009).…”

Section: Introductionmentioning

confidence: 99%

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LEF1/β-Catenin Complex Regulates Transcription of the Cav3.1 Calcium Channel Gene (Cacna1g) in Thalamic Neurons of the Adult Brain

Wisniewska

Misztal²,

Michowski³

et al. 2010

J. Neurosci.

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␤-Catenin, together with LEF1/TCF transcription factors, activates genes involved in the proliferation and differentiation of neuronal precursor cells. In mature neurons, ␤-catenin participates in dendritogenesis and synaptic function as a component of the cadherin cell adhesion complex. However, the transcriptional activity of ␤-catenin in these cells remains elusive. In the present study, we found that in the adult mouse brain, ␤-catenin and LEF1 accumulate in the nuclei of neurons specifically in the thalamus. The particular electrophysiological properties of thalamic neurons depend on T-type calcium channels. Cav3.1 is the predominant T-type channel subunit in the thalamus, and we hypothesized that the Cacna1g gene encoding Cav3.1 is a target of the LEF1/␤-catenin complex. We demonstrated that the expression of Cacna1g is high in the thalamus and is further increased in thalamic neurons treated in vitro with LiCl or WNT3A, activators of ␤-catenin. Luciferase reporter assays confirmed that the Cacna1G promoter is activated by LEF1 and ␤-catenin, and footprinting analysis revealed four LEF1 binding sites in the proximal region of this promoter. Chromatin immunoprecipitation demonstrated that the Cacna1g proximal promoter is occupied by ␤-catenin in vivo in the thalamus, but not in the hippocampus. Moreover, WNT3A stimulation enhanced T-type current in cultured thalamic neurons. Together, our data indicate that the LEF1/␤-catenin complex regulates transcription of Cacna1g and uncover a novel function for ␤-catenin in mature neurons. We propose that ␤-catenin contributes to neuronal excitability not only by a local action at the synapse but also by activating gene expression in thalamic neurons.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

LEF1/β-Catenin Complex Regulates Transcription of the Cav3.1 Calcium Channel Gene (Cacna1g) in Thalamic Neurons of the Adult Brain

Wisniewska

Misztal²,

Michowski³

et al. 2010

J. Neurosci.

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“…Through enhanced network activity, inputs sculpt den-dritic development by turning on the necessary molecular pathways (Libersat and Duch 2004). Multiple molecular pathways include the following: Rac1 shown to be involved in learningevoked neurogenesis (Haditsch et al 2013), the neural activity-induced immediate early gene Gadd45b (Ma et al 2009), b-catenin (Gao et al 2007), Notch (Breunig et al 2008), and TrkB (Bergami et al 2008;Danzer et al 2008), and DISC1 (Duan et al 2007). Clearly, additional investigations are required to better understand the mechanisms by which learning induces changes in neurogenesis.…”

Section: Mechanismsmentioning

confidence: 99%

Interaction between Neurogenesis and Hippocampal Memory System: New Vistas

Abrous

Wojtowicz

2015

Cold Spring Harb Perspect Biol

101

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During the last decade, the questions on the functionality of adult neurogenesis have changed their emphasis from if to how the adult-born neurons participate in a variety of memory processes. The emerging answers are complex because we are overwhelmed by a variety of behavioral tasks that apparently require new neurons to be performed optimally. With few exceptions, the hippocampal memory system seems to use the newly generated neurons for multiple roles. Adult neurogenesis has given the dentate gyrus new capabilities not previously thought possible within the scope of traditional synaptic plasticity. Looking at these new developments from the perspective of past discoveries, the science of adult neurogenesis has emerged from its initial phase of being, first, a surprising oddity and, later, exciting possibility, to the present state of being an integral part of mainstream neuroscience. The answers to many remaining questions regarding adult neurogenesis will come along only with our growing understanding of the functionality of the brain as a whole. This, in turn, will require integration of multiple levels of organization from molecules and cells to circuits and systems, ultimately resulting in comprehension of behavioral outcomes.

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“…Using conditional-knockout animals, a role of β-catenin on dendrite development of postnatally born hippocampal dentategyrus neurons was identified (Gao et al, 2007). β-catenin conditional-knockout animals also showed a mild phenotype in mood-and anxiety-related behavioural models (Gould et al, 2008).…”

Section: Brain Function Relies On the Establishment Of The Correct Pamentioning

confidence: 99%

Signalling by neurotrophins and hepatocyte growth factor regulates axon morphogenesis by differential β-catenin phosphorylation

David

Yeramian

Duñach

et al. 2008

Journal of Cell Science

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Tyrosine phosphorylation of β-catenin, a component of adhesion complexes and of the Wnt pathway, affects cell adhesion, migration and gene transcription. By reducing β-catenin availability using shRNA-mediated gene silencing or expression of intracellular N-cadherin, we show that β-catenin is required for axon growth downstream of brain-derived neurotrophic factor (BDNF) signalling and hepatocyte growth factor (HGF) signalling. We demonstrate that the receptor tyrosine kinases (RTKs) Trk and Met interact with and phosphorylate β-catenin. Stimulation of Trk receptors by neurotrophins (NTs) results in phosphorylation of β-catenin at residue Y654, and increased axon growth and branching. Conversely, pharmacological inhibition of Trk or expression of a Y654F mutant blocks these effects. β-catenin phosphorylated at Y654 colocalizes with the cytoskeleton at growth cones. However, HGF, which also increases axon growth and branching, induces β-catenin phosphorylation at Y142 and a nuclear localization. Interestingly, dominant-negative ΔN-TCF4 abolishes the effects of HGF in axon growth and branching, but not that of NTs. We conclude that NT- and HGF-signalling differentially phosphorylate β-catenin, targeting this protein to distinct compartments to regulate axon morphogenesis by TCF4-transcription-dependent and -independent mechanisms. These results place β-catenin downstream of growth-factor–RTK signalling in axon differentiation.

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Conditional Knock-Out of β-Cateninin Postnatal-Born Dentate Gyrus Granule Neurons Results in Dendritic Malformation

Cited by 93 publications

References 45 publications

LEF1/β-Catenin Complex Regulates Transcription of the Cav3.1 Calcium Channel Gene (Cacna1g) in Thalamic Neurons of the Adult Brain

LEF1/β-Catenin Complex Regulates Transcription of the Cav3.1 Calcium Channel Gene (Cacna1g) in Thalamic Neurons of the Adult Brain

Interaction between Neurogenesis and Hippocampal Memory System: New Vistas

Signalling by neurotrophins and hepatocyte growth factor regulates axon morphogenesis by differential β-catenin phosphorylation

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