TGF-β1 PROMOTES CEREBRAL CORTEX RADIAL GLIA-ASTROCYTE DIFFERENTIATION IN VIVO

The major neural stem cell population in the developing cerebral cortex is composed of the radial glial cells, which generate glial cells and neurons. The mechanisms that modulate the maintenance of the radial glia stem cell phenotype, or its differentiation, are not yet completely understood. We pr...

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Main Authors: Joice eStipursky, Daniel Francis Franco, Rômulo Sperdutto Dezonne, Ana Paula eBérgamo, Lays eSouza, Carolina eMoraes, Flavia Carvalho Alcantara Gomes
Format: Article
Language:English
Published: Frontiers Media S.A. 2014-11-01
Series:Frontiers in Cellular Neuroscience
Subjects:
Online Access:http://journal.frontiersin.org/Journal/10.3389/fncel.2014.00393/full
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author Joice eStipursky
Daniel Francis Franco
Rômulo Sperdutto Dezonne
Ana Paula eBérgamo
Lays eSouza
Carolina eMoraes
Flavia Carvalho Alcantara Gomes
author_facet Joice eStipursky
Daniel Francis Franco
Rômulo Sperdutto Dezonne
Ana Paula eBérgamo
Lays eSouza
Carolina eMoraes
Flavia Carvalho Alcantara Gomes
author_sort Joice eStipursky
collection DOAJ
description The major neural stem cell population in the developing cerebral cortex is composed of the radial glial cells, which generate glial cells and neurons. The mechanisms that modulate the maintenance of the radial glia stem cell phenotype, or its differentiation, are not yet completely understood. We previously demonstrated that the transforming growth factor-β1 (TGF-β1) promotes radial glia differentiation into astrocytes in vitro (Glia 2007; 55:1023-33) through activation of multiple canonical and non-canonical signaling pathways (Dev Neurosci 2012; 34:68-81). However, it remains unknown if TGF-β1 acts in radial glia-astrocyte differentiation in vivo. Here, we addressed the astrogliogenesis induced by TGF-β1 by using the intraventricular in utero injection in vivo approach. We show that injection of TGF-β1 in the lateral ventricles of E14,5 mice embryos resulted in radial glia fibers disorganization and premature gliogenesis, evidenced by appearance of GFAP positive cells in the cortical wall. These events were followed by decreased numbers of neurons in the cortical plate. Together, we also described that TGF-β1 actions are region-dependent, once radial glia cells from dorsal region of the cerebral cortex demonstrated to be more responsive to this cytokine compared with radial glia from lateral cortex either in vitro as well as in vivo. Our work demonstrated that TGF-β1 is a critical cytokine that regulates radial glia fate decision and differentiation into astrocytes in vitro and in vivo. We also suggest that radial glia cells are heterogeneous population that acts as distinct targets of TGF-β1 during cerebral cortex development.
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spelling doaj.art-ac20273fcebb4b6aa9a4998cbf3010ad2022-12-22T03:56:15ZengFrontiers Media S.A.Frontiers in Cellular Neuroscience1662-51022014-11-01810.3389/fncel.2014.00393120287TGF-β1 PROMOTES CEREBRAL CORTEX RADIAL GLIA-ASTROCYTE DIFFERENTIATION IN VIVOJoice eStipursky0Daniel Francis Franco1Rômulo Sperdutto Dezonne2Ana Paula eBérgamo3Lays eSouza4Carolina eMoraes5Flavia Carvalho Alcantara Gomes6Federal University of Rio de JaneiroFederal University of Rio de JaneiroFederal University of Rio de JaneiroFederal University of Rio de JaneiroFederal University of Rio de JaneiroFederal University of Rio de JaneiroFederal University of Rio de JaneiroThe major neural stem cell population in the developing cerebral cortex is composed of the radial glial cells, which generate glial cells and neurons. The mechanisms that modulate the maintenance of the radial glia stem cell phenotype, or its differentiation, are not yet completely understood. We previously demonstrated that the transforming growth factor-β1 (TGF-β1) promotes radial glia differentiation into astrocytes in vitro (Glia 2007; 55:1023-33) through activation of multiple canonical and non-canonical signaling pathways (Dev Neurosci 2012; 34:68-81). However, it remains unknown if TGF-β1 acts in radial glia-astrocyte differentiation in vivo. Here, we addressed the astrogliogenesis induced by TGF-β1 by using the intraventricular in utero injection in vivo approach. We show that injection of TGF-β1 in the lateral ventricles of E14,5 mice embryos resulted in radial glia fibers disorganization and premature gliogenesis, evidenced by appearance of GFAP positive cells in the cortical wall. These events were followed by decreased numbers of neurons in the cortical plate. Together, we also described that TGF-β1 actions are region-dependent, once radial glia cells from dorsal region of the cerebral cortex demonstrated to be more responsive to this cytokine compared with radial glia from lateral cortex either in vitro as well as in vivo. Our work demonstrated that TGF-β1 is a critical cytokine that regulates radial glia fate decision and differentiation into astrocytes in vitro and in vivo. We also suggest that radial glia cells are heterogeneous population that acts as distinct targets of TGF-β1 during cerebral cortex development.http://journal.frontiersin.org/Journal/10.3389/fncel.2014.00393/fullCerebral CortexNeurogenesisGliogenesisradial gliaTGF-β
spellingShingle Joice eStipursky
Daniel Francis Franco
Rômulo Sperdutto Dezonne
Ana Paula eBérgamo
Lays eSouza
Carolina eMoraes
Flavia Carvalho Alcantara Gomes
TGF-β1 PROMOTES CEREBRAL CORTEX RADIAL GLIA-ASTROCYTE DIFFERENTIATION IN VIVO
Frontiers in Cellular Neuroscience
Cerebral Cortex
Neurogenesis
Gliogenesis
radial glia
TGF-β
title TGF-β1 PROMOTES CEREBRAL CORTEX RADIAL GLIA-ASTROCYTE DIFFERENTIATION IN VIVO
title_full TGF-β1 PROMOTES CEREBRAL CORTEX RADIAL GLIA-ASTROCYTE DIFFERENTIATION IN VIVO
title_fullStr TGF-β1 PROMOTES CEREBRAL CORTEX RADIAL GLIA-ASTROCYTE DIFFERENTIATION IN VIVO
title_full_unstemmed TGF-β1 PROMOTES CEREBRAL CORTEX RADIAL GLIA-ASTROCYTE DIFFERENTIATION IN VIVO
title_short TGF-β1 PROMOTES CEREBRAL CORTEX RADIAL GLIA-ASTROCYTE DIFFERENTIATION IN VIVO
title_sort tgf β1 promotes cerebral cortex radial glia astrocyte differentiation in vivo
topic Cerebral Cortex
Neurogenesis
Gliogenesis
radial glia
TGF-β
url http://journal.frontiersin.org/Journal/10.3389/fncel.2014.00393/full
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