Essential Role of Linx/Islr2 in the Development of the Forebrain Anterior Commissure

Abstract Linx is a member of the leucine-rich repeat and immunoglobulin family of membrane proteins which has critical roles in the development of the peripheral nervous system and forebrain connectivity. A previous study showed that Linx is expressed in projection neurons in the cortex and in cells...

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Autores principales: Shaniya Abudureyimu, Naoya Asai, Atsushi Enomoto, Liang Weng, Hiroki Kobayashi, Xiaoze Wang, Chen Chen, Shinji Mii, Masahide Takahashi
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Publicado: Nature Portfolio 2018
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Acceso en línea:https://doaj.org/article/9220edffbbd24b4f971216f607abc8b5
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spelling oai:doaj.org-article:9220edffbbd24b4f971216f607abc8b52021-12-02T12:32:35ZEssential Role of Linx/Islr2 in the Development of the Forebrain Anterior Commissure10.1038/s41598-018-24064-02045-2322https://doaj.org/article/9220edffbbd24b4f971216f607abc8b52018-05-01T00:00:00Zhttps://doi.org/10.1038/s41598-018-24064-0https://doaj.org/toc/2045-2322Abstract Linx is a member of the leucine-rich repeat and immunoglobulin family of membrane proteins which has critical roles in the development of the peripheral nervous system and forebrain connectivity. A previous study showed that Linx is expressed in projection neurons in the cortex and in cells that comprise the passage to the prethalamus that form the internal capsule, indicating the involvement of Linx in axon guidance and cell-cell communication. In this study, we found that Linx-deficient mice develop severe hydrocephalus and die perinatally by unknown mechanisms. Importantly, mice heterozygous for the linx gene exhibited defects in the development of the anterior commissure in addition to hydrocephalus, indicating haploinsufficiency of the linx gene in forebrain development. In N1E-115 neuroblastoma cells and primary cultured hippocampal neurons, Linx depletion led to impaired neurite extension and an increase in cell body size. Consistent with this, but of unknown significance, we found that Linx interacts with and upregulates the activity of Rho-kinase, a modulator of many cellular processes including cytoskeletal organization. These data suggest a role for Linx in the regulation of complex forebrain connectivity, and future identification of its extracellular ligand(s) will help clarify this function.Shaniya AbudureyimuNaoya AsaiAtsushi EnomotoLiang WengHiroki KobayashiXiaoze WangChen ChenShinji MiiMasahide TakahashiNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 8, Iss 1, Pp 1-13 (2018)
institution DOAJ
collection DOAJ
language EN
topic Medicine
R
Science
Q
spellingShingle Medicine
R
Science
Q
Shaniya Abudureyimu
Naoya Asai
Atsushi Enomoto
Liang Weng
Hiroki Kobayashi
Xiaoze Wang
Chen Chen
Shinji Mii
Masahide Takahashi
Essential Role of Linx/Islr2 in the Development of the Forebrain Anterior Commissure
description Abstract Linx is a member of the leucine-rich repeat and immunoglobulin family of membrane proteins which has critical roles in the development of the peripheral nervous system and forebrain connectivity. A previous study showed that Linx is expressed in projection neurons in the cortex and in cells that comprise the passage to the prethalamus that form the internal capsule, indicating the involvement of Linx in axon guidance and cell-cell communication. In this study, we found that Linx-deficient mice develop severe hydrocephalus and die perinatally by unknown mechanisms. Importantly, mice heterozygous for the linx gene exhibited defects in the development of the anterior commissure in addition to hydrocephalus, indicating haploinsufficiency of the linx gene in forebrain development. In N1E-115 neuroblastoma cells and primary cultured hippocampal neurons, Linx depletion led to impaired neurite extension and an increase in cell body size. Consistent with this, but of unknown significance, we found that Linx interacts with and upregulates the activity of Rho-kinase, a modulator of many cellular processes including cytoskeletal organization. These data suggest a role for Linx in the regulation of complex forebrain connectivity, and future identification of its extracellular ligand(s) will help clarify this function.
format article
author Shaniya Abudureyimu
Naoya Asai
Atsushi Enomoto
Liang Weng
Hiroki Kobayashi
Xiaoze Wang
Chen Chen
Shinji Mii
Masahide Takahashi
author_facet Shaniya Abudureyimu
Naoya Asai
Atsushi Enomoto
Liang Weng
Hiroki Kobayashi
Xiaoze Wang
Chen Chen
Shinji Mii
Masahide Takahashi
author_sort Shaniya Abudureyimu
title Essential Role of Linx/Islr2 in the Development of the Forebrain Anterior Commissure
title_short Essential Role of Linx/Islr2 in the Development of the Forebrain Anterior Commissure
title_full Essential Role of Linx/Islr2 in the Development of the Forebrain Anterior Commissure
title_fullStr Essential Role of Linx/Islr2 in the Development of the Forebrain Anterior Commissure
title_full_unstemmed Essential Role of Linx/Islr2 in the Development of the Forebrain Anterior Commissure
title_sort essential role of linx/islr2 in the development of the forebrain anterior commissure
publisher Nature Portfolio
publishDate 2018
url https://doaj.org/article/9220edffbbd24b4f971216f607abc8b5
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