FoxP2 directly regulates the reelin receptor VLDLR developmentally and by singing

Iris Adam*, Ezequiel Mendoza, Ursula Kobalz, Sandra Wohlgemuth, Constance Scharff

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Resumé

Mutations of the transcription factor FOXP2 cause a severe speech and language disorder. In songbirds, FoxP2 is expressed in the medium spiny neurons (MSNs) of the avian basal ganglia song nucleus, Area X, which is crucial for song learning and adult song performance. Experimental downregulation of FoxP2 in Area X affects spine formation, prevents neuronal plasticity induced by social context and impairs song learning. Direct target genes of FoxP2 relevant for song learning and song production are unknown. Here we show that a lentivirally mediated FoxP2 knockdown in Area X of zebra finches downregulates the expression of VLDLR, one of the two reelin receptors. Zebra finch FoxP2 binds to the promoter of VLDLR and activates it, establishing VLDLR as a direct FoxP2 target. Consistent with these findings, VLDLR expression is co-regulated with FoxP2 as a consequence of adult singing and during song learning. We also demonstrate that knockdown of FoxP2 affects glutamatergic transmission at the corticostriatal MSN synapse. These data raise the possibility that the regulatory relationship between FoxP2 and VLDLR guides structural plasticity towards the subset of FoxP2-positive MSNs in an activity dependent manner via the reelin pathway.

OriginalsprogEngelsk
TidsskriftMolecular and Cellular Neuroscience
Vol/bind74
Sider (fra-til)96-105
ISSN1044-7431
DOI
StatusUdgivet - 2016
Udgivet eksterntJa

Fingeraftryk

Music
Equidae
Neurons
Down-Regulation
reelin receptor
Mutation

Citer dette

Adam, Iris ; Mendoza, Ezequiel ; Kobalz, Ursula ; Wohlgemuth, Sandra ; Scharff, Constance. / FoxP2 directly regulates the reelin receptor VLDLR developmentally and by singing. I: Molecular and Cellular Neuroscience. 2016 ; Bind 74. s. 96-105.
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title = "FoxP2 directly regulates the reelin receptor VLDLR developmentally and by singing",
abstract = "Mutations of the transcription factor FOXP2 cause a severe speech and language disorder. In songbirds, FoxP2 is expressed in the medium spiny neurons (MSNs) of the avian basal ganglia song nucleus, Area X, which is crucial for song learning and adult song performance. Experimental downregulation of FoxP2 in Area X affects spine formation, prevents neuronal plasticity induced by social context and impairs song learning. Direct target genes of FoxP2 relevant for song learning and song production are unknown. Here we show that a lentivirally mediated FoxP2 knockdown in Area X of zebra finches downregulates the expression of VLDLR, one of the two reelin receptors. Zebra finch FoxP2 binds to the promoter of VLDLR and activates it, establishing VLDLR as a direct FoxP2 target. Consistent with these findings, VLDLR expression is co-regulated with FoxP2 as a consequence of adult singing and during song learning. We also demonstrate that knockdown of FoxP2 affects glutamatergic transmission at the corticostriatal MSN synapse. These data raise the possibility that the regulatory relationship between FoxP2 and VLDLR guides structural plasticity towards the subset of FoxP2-positive MSNs in an activity dependent manner via the reelin pathway.",
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author = "Iris Adam and Ezequiel Mendoza and Ursula Kobalz and Sandra Wohlgemuth and Constance Scharff",
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FoxP2 directly regulates the reelin receptor VLDLR developmentally and by singing. / Adam, Iris; Mendoza, Ezequiel; Kobalz, Ursula; Wohlgemuth, Sandra; Scharff, Constance.

I: Molecular and Cellular Neuroscience, Bind 74, 2016, s. 96-105.

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

TY - JOUR

T1 - FoxP2 directly regulates the reelin receptor VLDLR developmentally and by singing

AU - Adam, Iris

AU - Mendoza, Ezequiel

AU - Kobalz, Ursula

AU - Wohlgemuth, Sandra

AU - Scharff, Constance

PY - 2016

Y1 - 2016

N2 - Mutations of the transcription factor FOXP2 cause a severe speech and language disorder. In songbirds, FoxP2 is expressed in the medium spiny neurons (MSNs) of the avian basal ganglia song nucleus, Area X, which is crucial for song learning and adult song performance. Experimental downregulation of FoxP2 in Area X affects spine formation, prevents neuronal plasticity induced by social context and impairs song learning. Direct target genes of FoxP2 relevant for song learning and song production are unknown. Here we show that a lentivirally mediated FoxP2 knockdown in Area X of zebra finches downregulates the expression of VLDLR, one of the two reelin receptors. Zebra finch FoxP2 binds to the promoter of VLDLR and activates it, establishing VLDLR as a direct FoxP2 target. Consistent with these findings, VLDLR expression is co-regulated with FoxP2 as a consequence of adult singing and during song learning. We also demonstrate that knockdown of FoxP2 affects glutamatergic transmission at the corticostriatal MSN synapse. These data raise the possibility that the regulatory relationship between FoxP2 and VLDLR guides structural plasticity towards the subset of FoxP2-positive MSNs in an activity dependent manner via the reelin pathway.

AB - Mutations of the transcription factor FOXP2 cause a severe speech and language disorder. In songbirds, FoxP2 is expressed in the medium spiny neurons (MSNs) of the avian basal ganglia song nucleus, Area X, which is crucial for song learning and adult song performance. Experimental downregulation of FoxP2 in Area X affects spine formation, prevents neuronal plasticity induced by social context and impairs song learning. Direct target genes of FoxP2 relevant for song learning and song production are unknown. Here we show that a lentivirally mediated FoxP2 knockdown in Area X of zebra finches downregulates the expression of VLDLR, one of the two reelin receptors. Zebra finch FoxP2 binds to the promoter of VLDLR and activates it, establishing VLDLR as a direct FoxP2 target. Consistent with these findings, VLDLR expression is co-regulated with FoxP2 as a consequence of adult singing and during song learning. We also demonstrate that knockdown of FoxP2 affects glutamatergic transmission at the corticostriatal MSN synapse. These data raise the possibility that the regulatory relationship between FoxP2 and VLDLR guides structural plasticity towards the subset of FoxP2-positive MSNs in an activity dependent manner via the reelin pathway.

KW - Birdsong

KW - FoxP2

KW - Gene regulation

KW - Synaptic transmission

KW - VLDLR

U2 - 10.1016/j.mcn.2016.04.002

DO - 10.1016/j.mcn.2016.04.002

M3 - Journal article

VL - 74

SP - 96

EP - 105

JO - Molecular and Cellular Neuroscience

JF - Molecular and Cellular Neuroscience

SN - 1044-7431

ER -