The polymicrogyria-associated GPR56 promoter preferentially drives gene expression in developing GABAergic neurons in common marmosets

Abstract GPR56, a member of the adhesion G protein-coupled receptor family, is abundantly expressed in cells of the developing cerebral cortex, including neural progenitor cells and developing neurons. The human GPR56 gene has multiple presumptive promoters that drive the expression of the GPR56 pro...

Descripción completa

Guardado en:

Detalles Bibliográficos
Autores principales:	Ayako Y. Murayama, Ken-ichiro Kuwako, Junko Okahara, Byoung-Il Bae, Misako Okuno, Hiromi Mashiko, Tomomi Shimogori, Christopher A. Walsh, Erika Sasaki, Hideyuki Okano
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2020
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/8805ff715f5d4543bdedcd95bd83ed87
Etiquetas:	Agregar Etiqueta Sin Etiquetas, Sea el primero en etiquetar este registro!

id	oai:doaj.org-article:8805ff715f5d4543bdedcd95bd83ed87
record_format	dspace
spelling	oai:doaj.org-article:8805ff715f5d4543bdedcd95bd83ed872021-12-02T16:18:04ZThe polymicrogyria-associated GPR56 promoter preferentially drives gene expression in developing GABAergic neurons in common marmosets10.1038/s41598-020-78608-42045-2322https://doaj.org/article/8805ff715f5d4543bdedcd95bd83ed872020-12-01T00:00:00Zhttps://doi.org/10.1038/s41598-020-78608-4https://doaj.org/toc/2045-2322Abstract GPR56, a member of the adhesion G protein-coupled receptor family, is abundantly expressed in cells of the developing cerebral cortex, including neural progenitor cells and developing neurons. The human GPR56 gene has multiple presumptive promoters that drive the expression of the GPR56 protein in distinct patterns. Similar to coding mutations of the human GPR56 gene that may cause GPR56 dysfunction, a 15-bp homozygous deletion in the cis-regulatory element upstream of the noncoding exon 1 of GPR56 (e1m) leads to the cerebral cortex malformation and epilepsy. To clarify the expression profile of the e1m promoter-driven GPR56 in primate brain, we generated a transgenic marmoset line in which EGFP is expressed under the control of the human minimal e1m promoter. In contrast to the endogenous GPR56 protein, which is highly enriched in the ventricular zone of the cerebral cortex, EGFP is mostly expressed in developing neurons in the transgenic fetal brain. Furthermore, EGFP is predominantly expressed in GABAergic neurons, whereas the total GPR56 protein is evenly expressed in both GABAergic and glutamatergic neurons, suggesting the GABAergic neuron-preferential activity of the minimal e1m promoter. These results indicate a possible pathogenic role for GABAergic neuron in the cerebral cortex of patients with GPR56 mutations.Ayako Y. MurayamaKen-ichiro KuwakoJunko OkaharaByoung-Il BaeMisako OkunoHiromi MashikoTomomi ShimogoriChristopher A. WalshErika SasakiHideyuki OkanoNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 10, Iss 1, Pp 1-13 (2020)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Ayako Y. Murayama Ken-ichiro Kuwako Junko Okahara Byoung-Il Bae Misako Okuno Hiromi Mashiko Tomomi Shimogori Christopher A. Walsh Erika Sasaki Hideyuki Okano The polymicrogyria-associated GPR56 promoter preferentially drives gene expression in developing GABAergic neurons in common marmosets
description	Abstract GPR56, a member of the adhesion G protein-coupled receptor family, is abundantly expressed in cells of the developing cerebral cortex, including neural progenitor cells and developing neurons. The human GPR56 gene has multiple presumptive promoters that drive the expression of the GPR56 protein in distinct patterns. Similar to coding mutations of the human GPR56 gene that may cause GPR56 dysfunction, a 15-bp homozygous deletion in the cis-regulatory element upstream of the noncoding exon 1 of GPR56 (e1m) leads to the cerebral cortex malformation and epilepsy. To clarify the expression profile of the e1m promoter-driven GPR56 in primate brain, we generated a transgenic marmoset line in which EGFP is expressed under the control of the human minimal e1m promoter. In contrast to the endogenous GPR56 protein, which is highly enriched in the ventricular zone of the cerebral cortex, EGFP is mostly expressed in developing neurons in the transgenic fetal brain. Furthermore, EGFP is predominantly expressed in GABAergic neurons, whereas the total GPR56 protein is evenly expressed in both GABAergic and glutamatergic neurons, suggesting the GABAergic neuron-preferential activity of the minimal e1m promoter. These results indicate a possible pathogenic role for GABAergic neuron in the cerebral cortex of patients with GPR56 mutations.
format	article
author	Ayako Y. Murayama Ken-ichiro Kuwako Junko Okahara Byoung-Il Bae Misako Okuno Hiromi Mashiko Tomomi Shimogori Christopher A. Walsh Erika Sasaki Hideyuki Okano
author_facet	Ayako Y. Murayama Ken-ichiro Kuwako Junko Okahara Byoung-Il Bae Misako Okuno Hiromi Mashiko Tomomi Shimogori Christopher A. Walsh Erika Sasaki Hideyuki Okano
author_sort	Ayako Y. Murayama
title	The polymicrogyria-associated GPR56 promoter preferentially drives gene expression in developing GABAergic neurons in common marmosets
title_short	The polymicrogyria-associated GPR56 promoter preferentially drives gene expression in developing GABAergic neurons in common marmosets
title_full	The polymicrogyria-associated GPR56 promoter preferentially drives gene expression in developing GABAergic neurons in common marmosets
title_fullStr	The polymicrogyria-associated GPR56 promoter preferentially drives gene expression in developing GABAergic neurons in common marmosets
title_full_unstemmed	The polymicrogyria-associated GPR56 promoter preferentially drives gene expression in developing GABAergic neurons in common marmosets
title_sort	polymicrogyria-associated gpr56 promoter preferentially drives gene expression in developing gabaergic neurons in common marmosets
publisher	Nature Portfolio
publishDate	2020
url	https://doaj.org/article/8805ff715f5d4543bdedcd95bd83ed87
work_keys_str_mv	AT ayakoymurayama thepolymicrogyriaassociatedgpr56promoterpreferentiallydrivesgeneexpressionindevelopinggabaergicneuronsincommonmarmosets AT kenichirokuwako thepolymicrogyriaassociatedgpr56promoterpreferentiallydrivesgeneexpressionindevelopinggabaergicneuronsincommonmarmosets AT junkookahara thepolymicrogyriaassociatedgpr56promoterpreferentiallydrivesgeneexpressionindevelopinggabaergicneuronsincommonmarmosets AT byoungilbae thepolymicrogyriaassociatedgpr56promoterpreferentiallydrivesgeneexpressionindevelopinggabaergicneuronsincommonmarmosets AT misakookuno thepolymicrogyriaassociatedgpr56promoterpreferentiallydrivesgeneexpressionindevelopinggabaergicneuronsincommonmarmosets AT hiromimashiko thepolymicrogyriaassociatedgpr56promoterpreferentiallydrivesgeneexpressionindevelopinggabaergicneuronsincommonmarmosets AT tomomishimogori thepolymicrogyriaassociatedgpr56promoterpreferentiallydrivesgeneexpressionindevelopinggabaergicneuronsincommonmarmosets AT christopherawalsh thepolymicrogyriaassociatedgpr56promoterpreferentiallydrivesgeneexpressionindevelopinggabaergicneuronsincommonmarmosets AT erikasasaki thepolymicrogyriaassociatedgpr56promoterpreferentiallydrivesgeneexpressionindevelopinggabaergicneuronsincommonmarmosets AT hideyukiokano thepolymicrogyriaassociatedgpr56promoterpreferentiallydrivesgeneexpressionindevelopinggabaergicneuronsincommonmarmosets AT ayakoymurayama polymicrogyriaassociatedgpr56promoterpreferentiallydrivesgeneexpressionindevelopinggabaergicneuronsincommonmarmosets AT kenichirokuwako polymicrogyriaassociatedgpr56promoterpreferentiallydrivesgeneexpressionindevelopinggabaergicneuronsincommonmarmosets AT junkookahara polymicrogyriaassociatedgpr56promoterpreferentiallydrivesgeneexpressionindevelopinggabaergicneuronsincommonmarmosets AT byoungilbae polymicrogyriaassociatedgpr56promoterpreferentiallydrivesgeneexpressionindevelopinggabaergicneuronsincommonmarmosets AT misakookuno polymicrogyriaassociatedgpr56promoterpreferentiallydrivesgeneexpressionindevelopinggabaergicneuronsincommonmarmosets AT hiromimashiko polymicrogyriaassociatedgpr56promoterpreferentiallydrivesgeneexpressionindevelopinggabaergicneuronsincommonmarmosets AT tomomishimogori polymicrogyriaassociatedgpr56promoterpreferentiallydrivesgeneexpressionindevelopinggabaergicneuronsincommonmarmosets AT christopherawalsh polymicrogyriaassociatedgpr56promoterpreferentiallydrivesgeneexpressionindevelopinggabaergicneuronsincommonmarmosets AT erikasasaki polymicrogyriaassociatedgpr56promoterpreferentiallydrivesgeneexpressionindevelopinggabaergicneuronsincommonmarmosets AT hideyukiokano polymicrogyriaassociatedgpr56promoterpreferentiallydrivesgeneexpressionindevelopinggabaergicneuronsincommonmarmosets
_version_	1718384180975370240

The polymicrogyria-associated GPR56 promoter preferentially drives gene expression in developing GABAergic neurons in common marmosets

Ejemplares similares