Satb2 regulates callosal projection neuron identity in the developing cerebral cortex

被引:487
作者
Alcamo, Elizabeth A. [2 ]
Chirivella, Laura [3 ,4 ]
Dautzenberg, Marcel [1 ]
Dobreva, Gergana [1 ]
Farinas, Isabel [3 ,4 ]
Grosschedl, Rudolf [1 ]
McConnell, Susan K. [2 ]
机构
[1] Max Planck Inst Immunobiol, D-79108 Freiburg, Germany
[2] Stanford Univ, Dept Biol, Stanford, CA 94305 USA
[3] Univ Valencia, Dept Biol Celular, Burjassot 46100, Spain
[4] Univ Valencia, Unidad Mixta CIPF UVEG, Burjassot 46100, Spain
关键词
D O I
10.1016/j.neuron.2007.12.012
中图分类号
Q189 [神经科学];
学科分类号
071006 ;
摘要
Satb2 is a DNA-binding protein that regulates chromatin organization and gene expression. In the developing brain, Satb2 is expressed in cortical neurons that extend axons across the corpus callosum. To assess the role of Satb2 in neurons, we analyzed mice in which the Satb2 locus was disrupted by insertion of a LacZ gene. In mutant mice, beta-galactosidase-labeled axons are absent from the corpus callosum and instead descend along the corticospinal tract. Stab2 mutant neurons acquire expression of Ctip2, a transcription factor that is necessary and sufficient for the extension of subcortical projections by cortical neurons. Conversely, ectopic expression of Satb2 in neural stem cells markedly decreases Ctip2 expression. Finally, we find that Satb2 binds directly to regulatory regions of Ctip2 and induces changes in chromatin structure. These data suggest that Satb2 functions as a repressor of Ctip2 and regulatory determinant of corticocortical connections in the developing cerebral cortex.
引用
收藏
页码:364 / 377
页数:14
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