The chromatin-remodeling protein ATRX is critical for neuronal survival during corticogenesis

Bérubé, Nathalie G., Mangelsdorf, Marie, Jagla, Magdalena, Vanderluit, Jackie, Garrick, David, Gibbons, Richard J., Higgs, Douglas R., Slack, Ruth S. and Picketts, David J. (2005) The chromatin-remodeling protein ATRX is critical for neuronal survival during corticogenesis. Journal of Clinical Investigation, 115 2: 258-267. doi:10.1172/JCI200522329

Author Bérubé, Nathalie G.
Mangelsdorf, Marie
Jagla, Magdalena
Vanderluit, Jackie
Garrick, David
Gibbons, Richard J.
Higgs, Douglas R.
Slack, Ruth S.
Picketts, David J.
Title The chromatin-remodeling protein ATRX is critical for neuronal survival during corticogenesis
Journal name Journal of Clinical Investigation   Check publisher's open access policy
ISSN 0021-9738
Publication date 2005-02
Sub-type Article (original research)
DOI 10.1172/JCI200522329
Open Access Status DOI
Volume 115
Issue 2
Start page 258
End page 267
Total pages 10
Editor Laurence A. Turka
Place of publication Ann Arbor, MI, United States
Publisher American Society for Clinical Investigation
Language eng
Subject 060410 Neurogenetics
Formatted abstract
Mutations in genes encoding chromatin-remodeling proteins, such as the ATRX gene, underlie a number of genetic disorders including several X-linked mental retardation syndromes; however, the role of these proteins in normal CNS development is unknown. Here, we used a conditional gene-targeting approach to inactivate Atrx, specifically in the forebrain of mice. Loss of ATRX protein caused widespread hypocellularity in the neocortex and hippocampus and a pronounced reduction in forebrain size. Neuronal “birthdating” confirmed that fewer neurons reached the superficial cortical layers, despite normal progenitor cell proliferation. The loss of cortical mass resulted from a 12-fold increase in neuronal apoptosis during early stages of corticogenesis in the mutant animals. Moreover, cortical progenitors isolated from Atrx-null mice undergo enhanced apoptosis upon differentiation. Taken together, our results indicate that ATRX is a critical mediator of cell survival during early neuronal differentiation. Thus, increased neuronal loss may contribute to the severe mental retardation observed in human patients.
Keyword ATRX
Q-Index Code C1
Q-Index Status Provisional Code
Institutional Status Non-UQ

Document type: Journal Article
Sub-type: Article (original research)
Collections: Excellence in Research Australia (ERA) - Collection
Queensland Brain Institute Publications
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