A positive autoregulatory loop of Jak-STAT signaling controls the onset of astrogliogenesis
A positive autoregulatory loop of Jak-STAT signaling controls the onset of astrogliogenesis
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DOI：
10.1038/nn1440
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发表时间：
2005-05-01
影响因子：
25
通讯作者：
Sun, YE
中科院分区：
文献类型：
--
作者：
He, F;Ge, WH;Sun, YE
在中枢神经系统的发育过程中，神经元和神经胶质细胞是以顺序方式产生的。尽管细胞因子诱导的JAK-STAT通路被认为调节星形胶质细胞的发生，但胶质形成较晚发生的机制尚不清楚。在这里，我们报道了Jak-STAT信号的总体活性在发育过程中在小鼠皮质生发区受到动态调节。因此，在神经源性因子高度表达的早期神经源性阶段，激活的STAT1/3和STAT介导的转录是可以忽略的。在神经胶质形成后期，神经源性因子的表达减少会导致STAT活性的强劲上升。我们的数据显示了一个正的自动调节环路，通过STAT1/3直接诱导JAK-STAT通路的各种成分的表达，以加强STAT信号并触发星形胶质细胞的形成。强制激活Jak-STAT信号导致早熟星形胶质细胞发生，抑制这一途径可阻止星形胶质细胞分化。这些观察表明，JAK-STAT通路的自动调节控制着星形胶质形成的开始。
During development of the CNS, neurons and glia are generated in a sequential manner. The mechanism underlying the later onset of gliogenesis is poorly understood, although the cytokine-induced Jak-STAT pathway has been postulated to regulate astrogliogenesis. Here, we report that the overall activity of Jak-STAT signaling is dynamically regulated in mouse cortical germinal zone during development. As such, activated STAT1/3 and STAT-mediated transcription are negligible at early, neurogenic stages, when neurogenic factors are highly expressed. At later, gliogenic periods, decreased expression of neurogenic factors causes robust elevation of STAT activity. Our data demonstrate a positive autoregulatory loop whereby STAT1/3 directly induces the expression of various components of the Jak-STAT pathway to strengthen STAT signaling and trigger astrogliogenesis. Forced activation of Jak-STAT signaling leads to precocious astrogliogenesis, and inhibition of this pathway blocks astrocyte differentiation. These observations suggest that autoregulation of the Jak-STAT pathway controls the onset of astrogliogenesis.