Satb2 regulates callosal projection neuron identity in the developing cerebral cortex
Satb2 regulates callosal projection neuron identity in the developing cerebral cortex
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DOI：
10.1016/j.neuron.2007.12.012
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发表时间：
2008-02-07
期刊：
影响因子：
16.2
通讯作者：
McConnell, Susan K.
中科院分区：
文献类型：
--
作者：
Alcamo, Elizabeth A.;Chirivella, Laura;McConnell, Susan K.
SATB2是一种调节染色质组织和基因表达的DNA结合蛋白。在发育中的大脑中，SATB2以皮质神经元的延伸，这些神经元延伸到callosum callosum。为了评估SATB2在神经元中的作用，我们分析了小鼠通过插入LACZ基因破坏SATB2基因座。在突变小鼠中，beta-半乳糖苷酶标记的轴突不含call体，而是沿着皮质脊髓束下降。 Stab2突变神经元获得CTIP2的表达，CTIP2是一种转录因子，足以延伸皮层神经元的皮层投影。相反，SATB2在神经干细胞中的异位表达显着降低了CTIP2的表达。最后，我们发现SATB2直接与CTIP2的调节区域结合，并诱导染色质结构的变化。这些数据表明SATB2充当CTIP2的阻遏物，并且在发育中的大脑皮层中的皮质皮质连接的调节决定因素。
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.