Long Non-Coding RNA Lacuna Regulates Neuronal Differentiation of Neural Stem Cells During Brain Development

Although long non-coding RNAs (lncRNAs) is one of the most abundant classes of RNAs encoded within the mammalian genome and are highly expressed in the adult brain, they remain poorly characterized and their roles in the brain development are not well understood. Here we identify the lncRNA Lacuna (...

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Autores principales:	Elpinickie Ninou, Artemis Michail, Panagiotis K. Politis
Formato:	article
Lenguaje:	EN
Publicado:	Frontiers Media S.A. 2021
Materias:	Tbr2/Eomes NONMMUT071331 non-coding genome lncRNAs KRAB/CRISPR/dCas9 Biology (General) QH301-705.5
Acceso en línea:	https://doaj.org/article/5d48f80597be4c68bc8a75e68059c01e
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spelling	oai:doaj.org-article:5d48f80597be4c68bc8a75e68059c01e2021-11-30T20:04:35ZLong Non-Coding RNA Lacuna Regulates Neuronal Differentiation of Neural Stem Cells During Brain Development2296-634X10.3389/fcell.2021.726857https://doaj.org/article/5d48f80597be4c68bc8a75e68059c01e2021-11-01T00:00:00Zhttps://www.frontiersin.org/articles/10.3389/fcell.2021.726857/fullhttps://doaj.org/toc/2296-634XAlthough long non-coding RNAs (lncRNAs) is one of the most abundant classes of RNAs encoded within the mammalian genome and are highly expressed in the adult brain, they remain poorly characterized and their roles in the brain development are not well understood. Here we identify the lncRNA Lacuna (also catalogued as NONMMUT071331.2 in NONCODE database) as a negative regulator of neuronal differentiation in the neural stem/progenitor cells (NSCs) during mouse brain development. In particular, we show that Lacuna is transcribed from a genomic locus near to the Tbr2/Eomes gene, a key player in the transition of intermediate progenitor cells towards the induction of neuronal differentiation. Lacuna RNA expression peaks at the developmental time window between E14.5 and E16.5, consistent with a role in neural differentiation. Overexpression experiments in ex vivo cultured NSCs from murine cortex suggest that Lacuna is sufficient to inhibit neuronal differentiation, induce the number of Nestin+ and Olig2+ cells, without affecting proliferation or apoptosis of NSCs. CRISPR/dCas9-KRAB mediated knockdown of Lacuna gene expression leads to the opposite phenotype by inducing neuronal differentiation and suppressing Nestin+ and Olig2+ cells, again without any effect on proliferation or apoptosis of NSCs. Interestingly, despite the negative action of Lacuna on neurogenesis, its knockdown inhibits Eomes transcription, implying a simultaneous, but opposite, role in facilitating the Eomes gene expression. Collectively, our observations indicate a critical function of Lacuna in the gene regulation networks that fine tune the neuronal differentiation in the mammalian NSCs.Elpinickie NinouElpinickie NinouArtemis MichailArtemis MichailPanagiotis K. PolitisFrontiers Media S.A.articleTbr2/EomesNONMMUT071331non-coding genomelncRNAsKRAB/CRISPR/dCas9Biology (General)QH301-705.5ENFrontiers in Cell and Developmental Biology, Vol 9 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Tbr2/Eomes NONMMUT071331 non-coding genome lncRNAs KRAB/CRISPR/dCas9 Biology (General) QH301-705.5
spellingShingle	Tbr2/Eomes NONMMUT071331 non-coding genome lncRNAs KRAB/CRISPR/dCas9 Biology (General) QH301-705.5 Elpinickie Ninou Elpinickie Ninou Artemis Michail Artemis Michail Panagiotis K. Politis Long Non-Coding RNA Lacuna Regulates Neuronal Differentiation of Neural Stem Cells During Brain Development
description	Although long non-coding RNAs (lncRNAs) is one of the most abundant classes of RNAs encoded within the mammalian genome and are highly expressed in the adult brain, they remain poorly characterized and their roles in the brain development are not well understood. Here we identify the lncRNA Lacuna (also catalogued as NONMMUT071331.2 in NONCODE database) as a negative regulator of neuronal differentiation in the neural stem/progenitor cells (NSCs) during mouse brain development. In particular, we show that Lacuna is transcribed from a genomic locus near to the Tbr2/Eomes gene, a key player in the transition of intermediate progenitor cells towards the induction of neuronal differentiation. Lacuna RNA expression peaks at the developmental time window between E14.5 and E16.5, consistent with a role in neural differentiation. Overexpression experiments in ex vivo cultured NSCs from murine cortex suggest that Lacuna is sufficient to inhibit neuronal differentiation, induce the number of Nestin+ and Olig2+ cells, without affecting proliferation or apoptosis of NSCs. CRISPR/dCas9-KRAB mediated knockdown of Lacuna gene expression leads to the opposite phenotype by inducing neuronal differentiation and suppressing Nestin+ and Olig2+ cells, again without any effect on proliferation or apoptosis of NSCs. Interestingly, despite the negative action of Lacuna on neurogenesis, its knockdown inhibits Eomes transcription, implying a simultaneous, but opposite, role in facilitating the Eomes gene expression. Collectively, our observations indicate a critical function of Lacuna in the gene regulation networks that fine tune the neuronal differentiation in the mammalian NSCs.
format	article
author	Elpinickie Ninou Elpinickie Ninou Artemis Michail Artemis Michail Panagiotis K. Politis
author_facet	Elpinickie Ninou Elpinickie Ninou Artemis Michail Artemis Michail Panagiotis K. Politis
author_sort	Elpinickie Ninou
title	Long Non-Coding RNA Lacuna Regulates Neuronal Differentiation of Neural Stem Cells During Brain Development
title_short	Long Non-Coding RNA Lacuna Regulates Neuronal Differentiation of Neural Stem Cells During Brain Development
title_full	Long Non-Coding RNA Lacuna Regulates Neuronal Differentiation of Neural Stem Cells During Brain Development
title_fullStr	Long Non-Coding RNA Lacuna Regulates Neuronal Differentiation of Neural Stem Cells During Brain Development
title_full_unstemmed	Long Non-Coding RNA Lacuna Regulates Neuronal Differentiation of Neural Stem Cells During Brain Development
title_sort	long non-coding rna lacuna regulates neuronal differentiation of neural stem cells during brain development
publisher	Frontiers Media S.A.
publishDate	2021
url	https://doaj.org/article/5d48f80597be4c68bc8a75e68059c01e
work_keys_str_mv	AT elpinickieninou longnoncodingrnalacunaregulatesneuronaldifferentiationofneuralstemcellsduringbraindevelopment AT elpinickieninou longnoncodingrnalacunaregulatesneuronaldifferentiationofneuralstemcellsduringbraindevelopment AT artemismichail longnoncodingrnalacunaregulatesneuronaldifferentiationofneuralstemcellsduringbraindevelopment AT artemismichail longnoncodingrnalacunaregulatesneuronaldifferentiationofneuralstemcellsduringbraindevelopment AT panagiotiskpolitis longnoncodingrnalacunaregulatesneuronaldifferentiationofneuralstemcellsduringbraindevelopment
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Long Non-Coding RNA Lacuna Regulates Neuronal Differentiation of Neural Stem Cells During Brain Development

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