Dynamics and function of CXCR4 in formation of the granule cell layer during hippocampal development

Abstract In the developing hippocampus, granule cell progenitors (GCPs) arising in the ventricular zone (VZ) migrate to the subpial region, and form the granule cell layer (GCL) of the dentate gyrus (DG). To understand the mechanism of GCL formation, we investigated the dynamics and function of CXCR...

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Autores principales:	Yuka Mimura-Yamamoto, Hiroshi Shinohara, Taichi Kashiwagi, Toru Sato, Seiji Shioda, Tatsunori Seki
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2017
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/cdf01b48975d4138a1f930b3f8b0a4c8
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spelling	oai:doaj.org-article:cdf01b48975d4138a1f930b3f8b0a4c82021-12-02T16:06:53ZDynamics and function of CXCR4 in formation of the granule cell layer during hippocampal development10.1038/s41598-017-05738-72045-2322https://doaj.org/article/cdf01b48975d4138a1f930b3f8b0a4c82017-07-01T00:00:00Zhttps://doi.org/10.1038/s41598-017-05738-7https://doaj.org/toc/2045-2322Abstract In the developing hippocampus, granule cell progenitors (GCPs) arising in the ventricular zone (VZ) migrate to the subpial region, and form the granule cell layer (GCL) of the dentate gyrus (DG). To understand the mechanism of GCL formation, we investigated the dynamics and function of CXCR4 which is expressed by the GCPs and is a receptor of the CXCL12 chemokine secreted by cells surrounding the DG. In the VZ, CXCR4 was expressed on the plasma membrane of the GCPs. During their migration and in the DG, CXCR4 was internalized and accumulated as puncta close to the centrosomes, Golgi apparatus, and lysosomes. Phosphatase analysis suggested that both phosphorylated and dephosphorylated CXCR4 exist on the plasma membrane, whereas CXCR4 in intracellular puncta was mainly dephosphorylated. Intraventricular administration of the CXCR4 antagonist AMD3100 resulted in the disappearance of CXCR4 expression from the intracellular puncta, and its appearance on the plasma membranes. Furthermore, AMD3100 treatment resulted in precocious differentiation, delayed migration, and ectopic GCPs. Taken together, these results suggest that during the development and migration of GCPs, CXCR4 on the plasma membrane is phosphorylated, internalized, sorted to the centrosomes, Golgi apparatus, and lysosomes, and functionally regulates GCP differentiation, migration and positioning.Yuka Mimura-YamamotoHiroshi ShinoharaTaichi KashiwagiToru SatoSeiji ShiodaTatsunori SekiNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 7, Iss 1, Pp 1-14 (2017)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Yuka Mimura-Yamamoto Hiroshi Shinohara Taichi Kashiwagi Toru Sato Seiji Shioda Tatsunori Seki Dynamics and function of CXCR4 in formation of the granule cell layer during hippocampal development
description	Abstract In the developing hippocampus, granule cell progenitors (GCPs) arising in the ventricular zone (VZ) migrate to the subpial region, and form the granule cell layer (GCL) of the dentate gyrus (DG). To understand the mechanism of GCL formation, we investigated the dynamics and function of CXCR4 which is expressed by the GCPs and is a receptor of the CXCL12 chemokine secreted by cells surrounding the DG. In the VZ, CXCR4 was expressed on the plasma membrane of the GCPs. During their migration and in the DG, CXCR4 was internalized and accumulated as puncta close to the centrosomes, Golgi apparatus, and lysosomes. Phosphatase analysis suggested that both phosphorylated and dephosphorylated CXCR4 exist on the plasma membrane, whereas CXCR4 in intracellular puncta was mainly dephosphorylated. Intraventricular administration of the CXCR4 antagonist AMD3100 resulted in the disappearance of CXCR4 expression from the intracellular puncta, and its appearance on the plasma membranes. Furthermore, AMD3100 treatment resulted in precocious differentiation, delayed migration, and ectopic GCPs. Taken together, these results suggest that during the development and migration of GCPs, CXCR4 on the plasma membrane is phosphorylated, internalized, sorted to the centrosomes, Golgi apparatus, and lysosomes, and functionally regulates GCP differentiation, migration and positioning.
format	article
author	Yuka Mimura-Yamamoto Hiroshi Shinohara Taichi Kashiwagi Toru Sato Seiji Shioda Tatsunori Seki
author_facet	Yuka Mimura-Yamamoto Hiroshi Shinohara Taichi Kashiwagi Toru Sato Seiji Shioda Tatsunori Seki
author_sort	Yuka Mimura-Yamamoto
title	Dynamics and function of CXCR4 in formation of the granule cell layer during hippocampal development
title_short	Dynamics and function of CXCR4 in formation of the granule cell layer during hippocampal development
title_full	Dynamics and function of CXCR4 in formation of the granule cell layer during hippocampal development
title_fullStr	Dynamics and function of CXCR4 in formation of the granule cell layer during hippocampal development
title_full_unstemmed	Dynamics and function of CXCR4 in formation of the granule cell layer during hippocampal development
title_sort	dynamics and function of cxcr4 in formation of the granule cell layer during hippocampal development
publisher	Nature Portfolio
publishDate	2017
url	https://doaj.org/article/cdf01b48975d4138a1f930b3f8b0a4c8
work_keys_str_mv	AT yukamimurayamamoto dynamicsandfunctionofcxcr4informationofthegranulecelllayerduringhippocampaldevelopment AT hiroshishinohara dynamicsandfunctionofcxcr4informationofthegranulecelllayerduringhippocampaldevelopment AT taichikashiwagi dynamicsandfunctionofcxcr4informationofthegranulecelllayerduringhippocampaldevelopment AT torusato dynamicsandfunctionofcxcr4informationofthegranulecelllayerduringhippocampaldevelopment AT seijishioda dynamicsandfunctionofcxcr4informationofthegranulecelllayerduringhippocampaldevelopment AT tatsunoriseki dynamicsandfunctionofcxcr4informationofthegranulecelllayerduringhippocampaldevelopment
_version_	1718384869746147328

Dynamics and function of CXCR4 in formation of the granule cell layer during hippocampal development

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