Lamin B1 levels modulate differentiation into neurons during embryonic corticogenesis

Abstract Lamin B1, a key component of the nuclear lamina, plays an important role in brain development. Ablation of endogenous Lamin B1 (Lmnb1) in the mouse strongly impairs embryonic brain development and corticogenesis. However, the mechanisms underlying these neurodevelopmental effects are unknow...

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Autores principales: Sameehan Mahajani, Caterina Giacomini, Federica Marinaro, Davide De Pietri Tonelli, Andrea Contestabile, Laura Gasparini
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Lenguaje:EN
Publicado: Nature Portfolio 2017
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Acceso en línea:https://doaj.org/article/946911ef6d464a83bd2e68edbd01b72d
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spelling oai:doaj.org-article:946911ef6d464a83bd2e68edbd01b72d2021-12-02T15:05:48ZLamin B1 levels modulate differentiation into neurons during embryonic corticogenesis10.1038/s41598-017-05078-62045-2322https://doaj.org/article/946911ef6d464a83bd2e68edbd01b72d2017-07-01T00:00:00Zhttps://doi.org/10.1038/s41598-017-05078-6https://doaj.org/toc/2045-2322Abstract Lamin B1, a key component of the nuclear lamina, plays an important role in brain development. Ablation of endogenous Lamin B1 (Lmnb1) in the mouse strongly impairs embryonic brain development and corticogenesis. However, the mechanisms underlying these neurodevelopmental effects are unknown. Here, we report that Lamin B1 levels modulate the differentiation of murine neural stem cells (NSCs) into neurons and astroglial-like cells. In vitro, endogenous Lmnb1 depletion favors NSC differentiation into glial fibrillar acidic protein (GFAP)-immunoreactive cells over neurons, while overexpression of human Lamin B1 (LMNB1) increases the proportion of neurons. In Lmnb1-null embryos, neurogenesis is reduced, while in vivo Lmnb1 silencing in mouse embryonic brain by in utero electroporation of a specific Lmnb1 sh-RNA results in aberrant cortical positioning of neurons and increased expression of the astrocytic marker GFAP in the cortex of 7-day old pups. Together, these results indicate that finely tuned levels of Lamin B1 are required for NSC differentiation into neurons, proper expression of the astrocytic marker GFAP and corticogenesis.Sameehan MahajaniCaterina GiacominiFederica MarinaroDavide De Pietri TonelliAndrea ContestabileLaura GaspariniNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 7, Iss 1, Pp 1-11 (2017)
institution DOAJ
collection DOAJ
language EN
topic Medicine
R
Science
Q
spellingShingle Medicine
R
Science
Q
Sameehan Mahajani
Caterina Giacomini
Federica Marinaro
Davide De Pietri Tonelli
Andrea Contestabile
Laura Gasparini
Lamin B1 levels modulate differentiation into neurons during embryonic corticogenesis
description Abstract Lamin B1, a key component of the nuclear lamina, plays an important role in brain development. Ablation of endogenous Lamin B1 (Lmnb1) in the mouse strongly impairs embryonic brain development and corticogenesis. However, the mechanisms underlying these neurodevelopmental effects are unknown. Here, we report that Lamin B1 levels modulate the differentiation of murine neural stem cells (NSCs) into neurons and astroglial-like cells. In vitro, endogenous Lmnb1 depletion favors NSC differentiation into glial fibrillar acidic protein (GFAP)-immunoreactive cells over neurons, while overexpression of human Lamin B1 (LMNB1) increases the proportion of neurons. In Lmnb1-null embryos, neurogenesis is reduced, while in vivo Lmnb1 silencing in mouse embryonic brain by in utero electroporation of a specific Lmnb1 sh-RNA results in aberrant cortical positioning of neurons and increased expression of the astrocytic marker GFAP in the cortex of 7-day old pups. Together, these results indicate that finely tuned levels of Lamin B1 are required for NSC differentiation into neurons, proper expression of the astrocytic marker GFAP and corticogenesis.
format article
author Sameehan Mahajani
Caterina Giacomini
Federica Marinaro
Davide De Pietri Tonelli
Andrea Contestabile
Laura Gasparini
author_facet Sameehan Mahajani
Caterina Giacomini
Federica Marinaro
Davide De Pietri Tonelli
Andrea Contestabile
Laura Gasparini
author_sort Sameehan Mahajani
title Lamin B1 levels modulate differentiation into neurons during embryonic corticogenesis
title_short Lamin B1 levels modulate differentiation into neurons during embryonic corticogenesis
title_full Lamin B1 levels modulate differentiation into neurons during embryonic corticogenesis
title_fullStr Lamin B1 levels modulate differentiation into neurons during embryonic corticogenesis
title_full_unstemmed Lamin B1 levels modulate differentiation into neurons during embryonic corticogenesis
title_sort lamin b1 levels modulate differentiation into neurons during embryonic corticogenesis
publisher Nature Portfolio
publishDate 2017
url https://doaj.org/article/946911ef6d464a83bd2e68edbd01b72d
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AT caterinagiacomini laminb1levelsmodulatedifferentiationintoneuronsduringembryoniccorticogenesis
AT federicamarinaro laminb1levelsmodulatedifferentiationintoneuronsduringembryoniccorticogenesis
AT davidedepietritonelli laminb1levelsmodulatedifferentiationintoneuronsduringembryoniccorticogenesis
AT andreacontestabile laminb1levelsmodulatedifferentiationintoneuronsduringembryoniccorticogenesis
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