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

@article{citeulike:2599458, 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.}, address = {Molecular Medicine Programs, Ottawa Health Research Institute, Ottawa, Ontario, Canada.}, author = {B\'{e}rub\'{e}, N. G. and Mangelsdorf, M. and Jagla, M. and Vanderluit, J. and Garrick, D. and Gibbons, R. J. and Higgs, D. R. and Slack, R. S. and Picketts, D. J.}, citeulike-article-id = {2599458}, citeulike-linkout-0 = {http://dx.doi.org/10.1172/JCI22329}, citeulike-linkout-1 = {http://view.ncbi.nlm.nih.gov/pubmed/15668733}, citeulike-linkout-2 = {http://www.hubmed.org/display.cgi?uids=15668733}, doi = {10.1172/JCI22329}, issn = {0021-9738}, journal = {J Clin Invest}, keywords = {microarray, ngf, pc12}, month = {February}, number = {2}, pages = {258--267}, posted-at = {2008-03-26 18:36:28}, priority = {2}, title = {The chromatin-remodeling protein ATRX is critical for neuronal survival during corticogenesis.}, url = {http://dx.doi.org/10.1172/JCI22329}, volume = {115}, year = {2005} }

TY - JOUR ID - citeulike:2599458 L3 - citeulike-article-id:2599458 N2 - 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. IS - 2 JF - J Clin Invest SN - 0021-9738 AD - Molecular Medicine Programs, Ottawa Health Research Institute, Ottawa, Ontario, Canada. EP - 267 TI - The chromatin-remodeling protein ATRX is critical for neuronal survival during corticogenesis. VL - 115 SP - 258 KW - microarray KW - ngf KW - pc12 AU - Bérubé, NG AU - Mangelsdorf, M AU - Jagla, M AU - Vanderluit, J AU - Garrick, D AU - Gibbons, RJ AU - Higgs, DR AU - Slack, RS AU - Picketts, DJ PY - 2005/02// UR - http://dx.doi.org/10.1172/JCI22329 ER -