Foxp2 controls synaptic wiring of corticostriatal circuits and vocal communication by opposing Mef2c

Chen, Yi-Chuan; Kuo, Hsiao Ying; Bornschein, Ulrich; Takahashi, Hiroshi; Chen, Shih Yun; Lu, Kuan Ming; Yang, Hao; Chen, Gui May; Lin, Jing Ruei; Lee, Yi Hsin; Chou, Yun Chia; Cheng, Sin Jhong; Chien, Ching‐Te; Enard, Wolfgang; Hevers, Wulf; Pääbo, Svante; Graybiel, Ann M.; Liu, Fu Chin

doi:10.1038/nn.4380

Cited by 101 publications

(117 citation statements)

References 47 publications

(72 reference statements)

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“…Since the expression of Ebf1 and Islet1 is common to Co cells and dSPN of the striatum, we examined whether these two cell types share additional molecular markers. Using E13.5 Islet1 Cre/+ ; R26 YFP/+ embryos, we confirmed that dSPN were labelled by immunostaining against transcription factors Ctip2 (Figure a–d, 93 ± 2%) and FoxP1 (Figure e–h; Arlotta et al, ; Chen et al, ; Chiu et al, ; Enard, ; Enard et al, ; Ferland, Cherry, Preware, Morrisey, & Walsh, ; Garcia‐Calero, Botella‐Lopez, Bahamonde, Perez‐Balaguer, & Martinez, ). In the Co, most YFP + cells expressed Ctip2 (Figure c) but almost none co‐expressed FoxP1 (Figure g) and its homolog FoxP2 (data not shown).…”

Section: Resultssupporting

confidence: 58%

Tangential migration of corridor guidepost neurons contributes to anxiety circuits

Tinterri

Deck

Keita

et al. 2017

J of Comparative Neurology

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In mammals, thalamic axons are guided internally toward their neocortical target by corridor (Co) neurons that act as axonal guideposts. The existence of Co-like neurons in non-mammalian species, in which thalamic axons do not grow internally, raised the possibility that Co cells might have an ancestral role. Here, we investigated the contribution of corridor (Co) cells to mature brain circuits using a combination of genetic fate-mapping and assays in mice. We unexpectedly found that Co neurons contribute to striatal-like projection neurons in the central extended amygdala. In particular, Co-like neurons participate in specific nuclei of the bed nucleus of the stria terminalis, which plays essential roles in anxiety circuits. Our study shows that Co neurons possess an evolutionary conserved role in anxiety circuits independently from an acquired guidepost function. It furthermore highlights that neurons can have multiple sequential functions during brain wiring and supports a general role of tangential migration in the building of subpallial circuits.

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Section: Resultssupporting

confidence: 58%

Tangential migration of corridor guidepost neurons contributes to anxiety circuits

Tinterri

Deck

Keita

et al. 2017

J of Comparative Neurology

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“…Mef2C is a transcription factor, which acts as a developmental brake on glutamatergic synapse formation and is regulated by Foxp2 (Chen et al 2016). However, we show that decreased excitatory activity in D1R-MSNs is present in both juvenile and adult Foxp2 S321X /+ mice.…”

Section: Discussionmentioning

confidence: 99%

Foxp2 loss of function increases striatal direct pathway inhibition via increased GABA release

et al. 2018

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Heterozygous mutations of the Forkhead-box protein 2 (FOXP2) gene in humans cause childhood apraxia of speech. Loss of Foxp2 in mice is known to affect striatal development and impair motor skills. However, it is unknown if striatal excitatory/inhibitory balance is affected during development and if the imbalance persists into adulthood. We investigated the effect of reduced Foxp2 expression, via a loss-of-function mutation, on striatal medium spiny neurons (MSNs). Our data show that heterozygous loss of Foxp2 decreases excitatory (AMPA receptor-mediated) and increases inhibitory (GABA receptor-mediated) currents in D1 dopamine receptor positive MSNs of juvenile and adult mice. Furthermore, reduced Foxp2 expression increases GAD67 expression, leading to both increased presynaptic content and release of GABA. Finally, pharmacological blockade of inhibitory activity in vivo partially rescues motor skill learning deficits in heterozygous Foxp2 mice. Our results suggest a novel role for Foxp2 in the regulation of striatal direct pathway activity through managing inhibitory drive.Electronic supplementary materialThe online version of this article (10.1007/s00429-018-1746-6) contains supplementary material, which is available to authorized users.

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“…Activated caspase‐3 immunostaining, which is a recommended and validated technique for detecting and quantifying apoptotic cells in tissue sections, 61 , 62 , 63 , 64 , 65 , 66 was performed similar to previous methods 66 . Briefly, paraffin‐embedded tissues were sectioned (~4 μm) onto slides, and hydrated through a series of xylene and alcohol baths.…”

Section: Methodsmentioning

confidence: 99%

CD8 T cells contribute to lacrimal gland pathology in the nonobese diabetic mouse model of Sjögren syndrome

et al. 2017

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Sjögren syndrome is an autoimmune disease characterized by targeted destruction of the lacrimal and salivary glands resulting in symptoms of severe ocular and oral dryness. Despite its prevalence, the mechanisms driving autoimmune manifestations are unclear. In patients and in the nonobese diabetic (NOD) mouse model of Sjögren syndrome, lymphocytic infiltrates consist of CD4 and CD8 T cells, although the role of CD8 T cells in disease pathogenesis has been largely unexplored. Here, we evaluated the contribution of CD8 T cells to lacrimal and salivary gland autoimmunity. Within the lacrimal and salivary glands of NOD mice, CD8 T cells were proliferating, expressed an activated phenotype, and produced inflammatory cytokines. Transfer of purified CD8 T cells isolated from the cervical lymph nodes (LN) of NOD mice into NOD-SCID recipients resulted in inflammation of the lacrimal glands, but was not sufficient to cause inflammation of the salivary glands. Lacrimal gland-infiltrating CD8 T cells displayed a cytotoxic phenotype, and epithelial cell damage in the lacrimal glands was observed in recipients of CD8 T cells regardless of the presence of CD4 T cells. Collectively, our results demonstrate that CD8 T cells play a pathogenic role in lacrimal gland autoimmunity. The gland-specific pathogenicity of CD8 T cells makes them a valuable resource to further understand the mechanisms that discriminate lacrimal versus salivary gland autoimmunity and for the development of new therapeutics that target the early stages of disease.

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Foxp2 controls synaptic wiring of corticostriatal circuits and vocal communication by opposing Mef2c

Cited by 101 publications

References 47 publications

Tangential migration of corridor guidepost neurons contributes to anxiety circuits

Tangential migration of corridor guidepost neurons contributes to anxiety circuits

Foxp2 loss of function increases striatal direct pathway inhibition via increased GABA release

CD8 T cells contribute to lacrimal gland pathology in the nonobese diabetic mouse model of Sjögren syndrome

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