The establishment of neuronal properties is controlled by Sox4 and Sox11
The establishment of neuronal properties is controlled by Sox4 and Sox11
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DOI：
10.1101/gad.403406
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发表时间：
2006-12-15
影响因子：
10.5
通讯作者：
Muhr, Jonas
中科院分区：
文献类型：
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作者：
Bergsland, Maria;Werme, Martin;Muhr, Jonas
神经发生的进展依赖于原基螺旋-环-螺旋（bHLH）转录因子。这些因子在未分化的神经干细胞中起作用，诱导细胞周期退出和神经源性程序的启动。然而，神经祖细胞中原膜bHLH蛋白的瞬时表达表明，神经元特征的表达必须依赖于原膜bHLH蛋白下游的先前未被探索的机制。在这里，我们发现HMG-box转录因子Sox4和Sox11对于建立泛神经元蛋白表达至关重要，它们位于原膜bHLH蛋白的下游。对一个神经元基因启动子的检测显示，Sox4和Sox11作为转录激活剂发挥其功能。有趣的是，Sox4和Sox11诱导神经元性状表达的能力与调节神经祖细胞退出细胞周期的机制无关。转录抑制蛋白REST/NRSF已被证明可以阻断未分化神经细胞中的神经元基因表达。我们现在发现REST/NRSF限制了Sox4和Sox11的表达，解释了REST/NRSF如何阻止神经元蛋白的早熟表达。总之，这些发现证明了Sox4和Sox11在神经元成熟过程中的核心调节作用，并在机制上将细胞周期退出与神经元特性的建立分开。
The progression of neurogenesis relies on proneural basic helix-loop-helix ( bHLH) transcription factors. These factors operate in undifferentiated neural stem cells and induce cell cycle exit and the initiation of a neurogenic program. However, the transient expression of proneural bHLH proteins in neural progenitors indicates that expression of neuronal traits must rely on previously unexplored mechanisms operating downstream from proneural bHLH proteins. Here we show that the HMG-box transcription factors Sox4 and Sox11 are of critical importance, downstream from proneural bHLH proteins, for the establishment of pan-neuronal protein expression. Examination of a neuronal gene promoter reveals that Sox4 and Sox11 exert their functions as transcriptional activators. Interestingly, the capacity of Sox4 and Sox11 to induce the expression of neuronal traits is independent of mechanisms regulating the exit of neural progenitors from the cell cycle. The transcriptional repressor protein REST/NRSF has been demonstrated to block neuronal gene expression in undifferentiated neural cells. We now show that REST/NRSF restricts the expression of Sox4 and Sox11, explaining how REST/NRSF can prevent precocious expression of neuronal proteins. Together, these findings demonstrate a central regulatory role of Sox4 and Sox11 during neuronal maturation and mechanistically separate cell cycle withdrawal from the establishment of neuronal properties.