Conditional gene ablation of Stat3 reveals differential signaling requirements for survival of motoneurons during development and after nerve injury in the adult.
Conditional gene ablation of Stat3 reveals differential signaling requirements for survival of motoneurons during development and after nerve injury in the adult.
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STAT3的条件基因消融揭示了成人发育过程和神经损伤后运动神经元存活的差异信号传导要求。
DOI：
10.1083/jcb.200107009
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发表时间：
2002-01-21
影响因子：
7.8
通讯作者：
Sendtner, Michael
中科院分区：
文献类型：
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作者：
Schweizer, Ulrich;Gunnersen, Jennifer;Karch, Christoph;Wiese, Stefan;Holtmann, Bettina;Takeda, Kiyoshi;Akira, Shizuo;Sendtner, Michael
睫状神经营养因子（CNTF）/白血病抑制因子（LIF）/心肌营养素基因家族的成员是胚胎和受损运动神经元的有效存活因子。这些因子通过涉及gp 130和LIFR-β的受体复合物起作用，并且配体结合导致各种信号传导途径的激活，包括Stat 3的磷酸化。通过Cre介导的运动神经元基因消融研究了Stat 3在小鼠神经元存活中的作用。Cre在神经丝轻链（NF-L）启动子下表达，在E12左右开始，此时这些神经元变得依赖于神经营养支持。在NF-L-Cre; Stat 3flox/KO小鼠中，在自然发生细胞死亡的胚胎期运动神经元的损失没有增强，尽管从这些小鼠中分离的运动神经元需要更高浓度的CNTF以在培养中获得最大存活。相反，运动神经元的生存显着减少面神经损伤后，在成人。然而，这些神经元可以通过添加神经营养因子（包括CNTF）来拯救。Stat 3是上调受损运动神经元中Reg-2和Bcl-xl表达所必需的。我们的数据表明，Stat 3激活起着至关重要的作用，运动神经元的生存神经损伤后，在出生后的生活，但在胚胎发育过程中，表明运动神经元的生存信号的要求在成熟过程中的变化。
Members of the ciliary neurotrophic factor (CNTF)/leukemia inhibitory factor (LIF)/cardiotrophin gene family are potent survival factors for embryonic and lesioned motoneurons. These factors act via receptor complexes involving gp130 and LIFR-β and ligand binding leads to activation of various signaling pathways, including phosphorylation of Stat3. The role of Stat3 in neuronal survival was investigated in mice by Cre-mediated gene ablation in motoneurons. Cre is expressed under the neurofilament light chain (NF-L) promoter, starting around E12 when these neurons become dependent on neurotrophic support. Loss of motoneurons during the embryonic period of naturally occurring cell death is not enhanced in NF-L–Cre; Stat3flox/KO mice although motoneurons isolated from these mice need higher concentrations of CNTF for maximal survival in culture. In contrast, motoneuron survival is significantly reduced after facial nerve lesion in the adult. These neurons, however, can be rescued by the addition of neurotrophic factors, including CNTF. Stat3 is essential for upregulation of Reg-2 and Bcl-xl expression in lesioned motoneurons. Our data show that Stat3 activation plays an essential role for motoneuron survival after nerve lesion in postnatal life but not during embryonic development, indicating that signaling requirements for motoneuron survival change during maturation.