Non-cell-autonomous action of STAT3 in maintenance of neural precursor cells in the mouse neocortex
Non-cell-autonomous action of STAT3 in maintenance of neural precursor cells in the mouse neocortex
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DOI：
10.1242/dev.02419
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发表时间：
2006-07
期刊：
影响因子：
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通讯作者：
T. Yoshimatsu;Daichi Kawaguchi;Koji Oishi;K. Takeda;S. Akira;Norihisa Masuyama;Y. Gotoh
中科院分区：
文献类型：
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作者：
T. Yoshimatsu;Daichi Kawaguchi;Koji Oishi;K. Takeda;S. Akira;Norihisa Masuyama;Y. Gotoh
转录因子STAT 3在小鼠新皮层的出生后发育过程中促进神经前体细胞（NPC）的星形胶质细胞分化，但很少有人知道STAT 3在胚胎新皮层中的可能作用。我们现在发现STAT 3在小鼠胚胎新皮质的NPC中表达，并且JAK-STAT 3信号通路在成纤维细胞生长因子2维持NPC中起着重要作用。有条件的删除STAT 3基因的NPC降低其能力，形成神经球在体外，以及促进神经元分化在体外和体内。此外，STAT 3被发现以非细胞自主的方式维持NPC在未分化状态。Notch配体Delta-like 1（DLL 1）的STAT 3依赖性表达似乎解释了STAT 3对NPC维持的非细胞自主作用，因为通过RNA干扰敲低DLL 1或用γ-分泌酶抑制剂抑制Notch激活可以消除STAT 3对神经球形成的增强作用。我们的研究结果揭示了JAK-STAT 3和DLL 1-Notch信号通路之间先前未被认识的相互作用机制，以及这种相互作用在早期新皮层发育过程中维持NPC的关键作用。
The transcription factor STAT3 promotes astrocytic differentiation of neural precursor cells (NPCs) during postnatal development of the mouse neocortex, but little has been known of the possible role of STAT3 in the embryonic neocortex. We now show that STAT3 is expressed in NPCs of the mouse embryonic neocortex and that the JAK-STAT3 signaling pathway plays an essential role in the maintenance of NPCs by fibroblast growth factor 2. Conditional deletion of the STAT3 gene in NPCs reduced their capacity to form neurospheres in vitro, as well as promoted neuronal differentiation both in vitro and in vivo. Furthermore, STAT3 was found to maintain NPCs in the undifferentiated state in a non-cell-autonomous manner. STAT3-dependent expression of the Notch ligand Delta-like1 (DLL1) appears to account for the non-cell-autonomous effect of STAT3 on NPC maintenance, as knockdown of DLL1 by RNA interference or inhibition of Notch activation with a γ-secretase inhibitor abrogated the enhancement of neurosphere formation by STAT3. Our results reveal a previously unrecognized mechanism of interaction between the JAK-STAT3 and DLL1-Notch signaling pathways, as well as a pivotal role for this interaction in maintenance of NPCs during early neocortical development.