GLI3 Is Required for OLIG2+ Progeny Production in Adult Dorsal Neural Stem Cells

The ventricular–subventricular zone (V-SVZ) is a postnatal germinal niche. It holds a large population of neural stem cells (NSCs) that generate neurons and oligodendrocytes for the olfactory bulb and (primarily) the corpus callosum, respectively. These NSCs are heterogeneous and generate different...

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Main Authors: Rebecca J. Embalabala, Asa A. Brockman, Amanda R. Jurewicz, Jennifer A. Kong, Kaitlyn Ryan, Cristina D. Guinto, Arturo Álvarez-Buylla, Chin Chiang, Rebecca A. Ihrie
Format: Article
Language:English
Published: MDPI AG 2022-01-01
Series:Cells
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Online Access:https://www.mdpi.com/2073-4409/11/2/218
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author Rebecca J. Embalabala
Asa A. Brockman
Amanda R. Jurewicz
Jennifer A. Kong
Kaitlyn Ryan
Cristina D. Guinto
Arturo Álvarez-Buylla
Chin Chiang
Rebecca A. Ihrie
author_facet Rebecca J. Embalabala
Asa A. Brockman
Amanda R. Jurewicz
Jennifer A. Kong
Kaitlyn Ryan
Cristina D. Guinto
Arturo Álvarez-Buylla
Chin Chiang
Rebecca A. Ihrie
author_sort Rebecca J. Embalabala
collection DOAJ
description The ventricular–subventricular zone (V-SVZ) is a postnatal germinal niche. It holds a large population of neural stem cells (NSCs) that generate neurons and oligodendrocytes for the olfactory bulb and (primarily) the corpus callosum, respectively. These NSCs are heterogeneous and generate different types of neurons depending on their location. Positional identity among NSCs is thought to be controlled in part by intrinsic pathways. However, extrinsic cell signaling through the secreted ligand Sonic hedgehog (Shh) is essential for neurogenesis in both the dorsal and ventral V-SVZ. Here we used a genetic approach to investigate the role of the transcription factors GLI2 and GLI3 in the proliferation and cell fate of dorsal and ventral V-SVZ NSCs. We find that while GLI3 is expressed in stem cell cultures from both dorsal and ventral V-SVZ, the repressor form of GLI3 is more abundant in dorsal V-SVZ. Despite this high dorsal expression and the requirement for other Shh pathway members, GLI3 loss affects the generation of ventrally-, but not dorsally-derived olfactory interneurons in vivo and does not affect trilineage differentiation in vitro. However, loss of GLI3 in the adult dorsal V-SVZ in vivo results in decreased numbers of OLIG2-expressing progeny, indicating a role in gliogenesis.
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spelling doaj.art-a0ae46c327a44206b07e0cfd7199e0042023-11-23T13:17:53ZengMDPI AGCells2073-44092022-01-0111221810.3390/cells11020218GLI3 Is Required for OLIG2+ Progeny Production in Adult Dorsal Neural Stem CellsRebecca J. Embalabala0Asa A. Brockman1Amanda R. Jurewicz2Jennifer A. Kong3Kaitlyn Ryan4Cristina D. Guinto5Arturo Álvarez-Buylla6Chin Chiang7Rebecca A. Ihrie8Department of Cell & Developmental Biology, Vanderbilt University School of Medicine, Nashville, TN 37232, USADepartment of Cell & Developmental Biology, Vanderbilt University School of Medicine, Nashville, TN 37232, USADepartment of Cell & Developmental Biology, Vanderbilt University School of Medicine, Nashville, TN 37232, USADepartment of Cell & Developmental Biology, Vanderbilt University School of Medicine, Nashville, TN 37232, USADepartment of Cell & Developmental Biology, Vanderbilt University School of Medicine, Nashville, TN 37232, USADepartment of Neurological Surgery, University of California—San Francisco, San Francisco, CA 94143, USADepartment of Neurological Surgery, University of California—San Francisco, San Francisco, CA 94143, USADepartment of Cell & Developmental Biology, Vanderbilt University School of Medicine, Nashville, TN 37232, USADepartment of Cell & Developmental Biology, Vanderbilt University School of Medicine, Nashville, TN 37232, USAThe ventricular–subventricular zone (V-SVZ) is a postnatal germinal niche. It holds a large population of neural stem cells (NSCs) that generate neurons and oligodendrocytes for the olfactory bulb and (primarily) the corpus callosum, respectively. These NSCs are heterogeneous and generate different types of neurons depending on their location. Positional identity among NSCs is thought to be controlled in part by intrinsic pathways. However, extrinsic cell signaling through the secreted ligand Sonic hedgehog (Shh) is essential for neurogenesis in both the dorsal and ventral V-SVZ. Here we used a genetic approach to investigate the role of the transcription factors GLI2 and GLI3 in the proliferation and cell fate of dorsal and ventral V-SVZ NSCs. We find that while GLI3 is expressed in stem cell cultures from both dorsal and ventral V-SVZ, the repressor form of GLI3 is more abundant in dorsal V-SVZ. Despite this high dorsal expression and the requirement for other Shh pathway members, GLI3 loss affects the generation of ventrally-, but not dorsally-derived olfactory interneurons in vivo and does not affect trilineage differentiation in vitro. However, loss of GLI3 in the adult dorsal V-SVZ in vivo results in decreased numbers of OLIG2-expressing progeny, indicating a role in gliogenesis.https://www.mdpi.com/2073-4409/11/2/218ventricular–subventricular zone (V-SVZ)neurogenesisSonic hedgehog (Shh)oligodendrocytesGli3radial glial cells
spellingShingle Rebecca J. Embalabala
Asa A. Brockman
Amanda R. Jurewicz
Jennifer A. Kong
Kaitlyn Ryan
Cristina D. Guinto
Arturo Álvarez-Buylla
Chin Chiang
Rebecca A. Ihrie
GLI3 Is Required for OLIG2+ Progeny Production in Adult Dorsal Neural Stem Cells
Cells
ventricular–subventricular zone (V-SVZ)
neurogenesis
Sonic hedgehog (Shh)
oligodendrocytes
Gli3
radial glial cells
title GLI3 Is Required for OLIG2+ Progeny Production in Adult Dorsal Neural Stem Cells
title_full GLI3 Is Required for OLIG2+ Progeny Production in Adult Dorsal Neural Stem Cells
title_fullStr GLI3 Is Required for OLIG2+ Progeny Production in Adult Dorsal Neural Stem Cells
title_full_unstemmed GLI3 Is Required for OLIG2+ Progeny Production in Adult Dorsal Neural Stem Cells
title_short GLI3 Is Required for OLIG2+ Progeny Production in Adult Dorsal Neural Stem Cells
title_sort gli3 is required for olig2 progeny production in adult dorsal neural stem cells
topic ventricular–subventricular zone (V-SVZ)
neurogenesis
Sonic hedgehog (Shh)
oligodendrocytes
Gli3
radial glial cells
url https://www.mdpi.com/2073-4409/11/2/218
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