Protooncogene Ski cooperates with the chromatin-remodeling factor Satb2 in specifying callosal neurons
Protooncogene Ski cooperates with the chromatin-remodeling factor Satb2 in specifying callosal neurons
复制标题
DOI：
10.1073/pnas.1108718109
复制
发表时间：
2012-02-28
影响因子：
11.1
通讯作者：
Atanasoski, Suzana
中科院分区：
文献类型：
--
作者：
Baranek, Constanze;Dittrich, Manuela;Atanasoski, Suzana
对从神经干细胞到皮质投射神经元的分子程序的初步见解正在出现。转录调节因子Ski的缺失与人类1 p36缺失综合征有关，该综合征包括中枢神经系统缺陷。在这里，我们报告的关键作用滑雪在维护的神经干细胞池和规范的胼胝体神经元。滑雪缺陷胼胝体神经元失去了他们的身份和异位表达转录因子Ctip 2。错误指定的胼胝体神经元在很大程度上不能形成胼胝体，而是将它们的轴突重定向到皮层下的目标。我们确定的染色质重塑因子Satb 2作为滑雪的合作伙伴，并表明，这两种蛋白质所需的转录抑制Ctip 2在胼胝体神经元。我们提出了一个模型，其中Satb 2招聘滑雪Ctip 2基因座，滑雪吸引组蛋白脱乙酰酶，从而使功能性核小体重塑和脱乙酰酶阻遏物复合物的形成。我们的研究结果建立了一个中心的作用Ski-Satb 2的相互作用在调节胼胝体神经元规格的转录机制。
First insights into the molecular programs orchestrating the progression from neural stem cells to cortical projection neurons are emerging. Loss of the transcriptional regulator Ski has been linked to the human 1p36 deletion syndrome, which includes central nervous system defects. Here, we report critical roles for Ski in the maintenance of the neural stem cell pool and the specification of callosal neurons. Ski-deficient callosal neurons lose their identity and ectopically express the transcription factor Ctip2. The misspecified callosal neurons largely fail to form the corpus callosum and instead redirect their axons toward subcortical targets. We identify the chromatin-remodeling factor Satb2 as a partner of Ski, and show that both proteins are required for transcriptional repression of Ctip2 in callosal neurons. We propose a model in which Satb2 recruits Ski to the Ctip2 locus, and Ski attracts histone deacetylases, thereby enabling the formation of a functional nucleosome remodeling and deacetylase repressor complex. Our findings establish a central role for Ski-Satb2 interactions in regulating transcriptional mechanisms of callosal neuron specification.