hGFAP-Positive Stem Cells Depend on Brg1 for Proper Formation of Cerebral and Cerebellar Structures
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hGFAP-Positive Stem Cells Depend on Brg1 for Proper Formation of Cerebral and Cerebellar Structures. / Holdhof, Dörthe; Schoof, Melanie; Hellwig, Malte; Holdhof, Niels Hendrik; Niesen, Judith; Schüller, Ulrich.
in: CEREB CORTEX, Jahrgang 30, Nr. 3, 14.03.2020, S. 1382-1392.Publikationen: SCORING: Beitrag in Fachzeitschrift/Zeitung › SCORING: Zeitschriftenaufsatz › Forschung › Begutachtung
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T1 - hGFAP-Positive Stem Cells Depend on Brg1 for Proper Formation of Cerebral and Cerebellar Structures
AU - Holdhof, Dörthe
AU - Schoof, Melanie
AU - Hellwig, Malte
AU - Holdhof, Niels Hendrik
AU - Niesen, Judith
AU - Schüller, Ulrich
N1 - © The Author(s) 2019. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permission@oup.com.
PY - 2020/3/14
Y1 - 2020/3/14
N2 - Brahma-related gene 1 (Brg1) is one of the two mutually exclusive catalytic subunits of the SWItch/sucrose nonfermentable (SWI/SNF) chromatin remodeling complex. Several roles of Brg1 have been described including acting as a tumor suppressor but also functioning in neural stem cell (NSC) maintenance, neural crest development, or differentiation of oligodendrocytes and Schwann cells. Here, we generated human glial fibrillary acidic protein (hGFAP)-cre::Brg1fl/fl mice to analyze the function of Brg1 in multipotential NSCs during late stages of neural development. hGFAP-cre::Brg1fl/fl mice died approximately 2 weeks after birth. Macroscopic examination revealed a severe hydrocephalus and a decreased brain weight caused by the loss of Brg1. The cerebellum of hGFAP-cre::Brg1fl/fl mice displayed disorganized cortical layers as well as a massive hypoplasia due to a dramatically reduced number of granule neurons. The cerebrum presented with less proliferative and more apoptotic precursor cells in the subventricular zone (SVZ). Furthermore, the cerebral cortex stood out with significantly thinned upper layers and with impressive dendrite pathology. Finally, the hippocampus was severely underdeveloped with only a sparse number of detectable neurons. We conclude that NSCs depend on Brg1 to give rise to major essential brain structures including the cerebellum, the cerebral cortex, and the hippocampus.
AB - Brahma-related gene 1 (Brg1) is one of the two mutually exclusive catalytic subunits of the SWItch/sucrose nonfermentable (SWI/SNF) chromatin remodeling complex. Several roles of Brg1 have been described including acting as a tumor suppressor but also functioning in neural stem cell (NSC) maintenance, neural crest development, or differentiation of oligodendrocytes and Schwann cells. Here, we generated human glial fibrillary acidic protein (hGFAP)-cre::Brg1fl/fl mice to analyze the function of Brg1 in multipotential NSCs during late stages of neural development. hGFAP-cre::Brg1fl/fl mice died approximately 2 weeks after birth. Macroscopic examination revealed a severe hydrocephalus and a decreased brain weight caused by the loss of Brg1. The cerebellum of hGFAP-cre::Brg1fl/fl mice displayed disorganized cortical layers as well as a massive hypoplasia due to a dramatically reduced number of granule neurons. The cerebrum presented with less proliferative and more apoptotic precursor cells in the subventricular zone (SVZ). Furthermore, the cerebral cortex stood out with significantly thinned upper layers and with impressive dendrite pathology. Finally, the hippocampus was severely underdeveloped with only a sparse number of detectable neurons. We conclude that NSCs depend on Brg1 to give rise to major essential brain structures including the cerebellum, the cerebral cortex, and the hippocampus.
U2 - 10.1093/cercor/bhz173
DO - 10.1093/cercor/bhz173
M3 - SCORING: Journal article
C2 - 31504276
VL - 30
SP - 1382
EP - 1392
JO - CEREB CORTEX
JF - CEREB CORTEX
SN - 1047-3211
IS - 3
ER -
