AKT signaling mediates IGF-I survival actions on otic neural progenitors.
AKT signaling mediates IGF-I survival actions on otic neural progenitors.
复制标题
DOI：
10.1371/journal.pone.0030790
复制
发表时间：
2012
期刊：
影响因子：
3.7
通讯作者：
Sanchez-Calderon H
中科院分区：
文献类型：
--
作者：
Aburto MR;Magariños M;Leon Y;Varela-Nieto I;Sanchez-Calderon H
耳神经元和感觉细胞来源于共同的祖细胞，其向成熟细胞的转变需要细胞存活、增殖和分化程序的协调。有丝分裂后的神经元的神经营养支持和存活已被深入研究，但在未成熟的增殖性耳神经母细胞的程序性细胞死亡的调节的基础仍然知之甚少。蛋白激酶AKT作为一个节点，在控制细胞存活和细胞周期进程中发挥关键作用。AKT被营养因子激活，包括胰岛素样生长因子I（IGF-I），通过磷脂酰肌醇3-激酶（PI 3 K）产生第二信使磷脂酰肌醇3-磷酸。在这里，我们研究了胰岛素样生长因子依赖性激活的PI 3 K-AKT通路在维持耳神经母细胞中的作用。通过使用鸡（原鸡）耳泡和声前庭神经节，蛋白质印迹，免疫组织化学和原位杂交的器官型培养物的组合，我们表明，IGF-I激活AKT保护神经祖细胞程序性细胞死亡。IGF-I维持耳神经母细胞处于未分化和增殖状态，其特征在于叉头框M1（FoxM 1）转录因子的上调。相比之下，我们的研究结果表明，有丝分裂后的p27 Kip阳性神经元成为IGF-I独立的，因为他们延长他们的神经元的过程。神经元逐渐减少其Igf 1 r的表达，而增加神经营养因子受体TrkC的表达。在早期内耳发育的耳神经元祖细胞阶段，增殖性耳神经母细胞依赖于IGF-I对PI 3 K-AKT通路的激活以存活。
Otic neurons and sensory cells derive from common progenitors whose transition into mature cells requires the coordination of cell survival, proliferation and differentiation programmes. Neurotrophic support and survival of post-mitotic otic neurons have been intensively studied, but the bases underlying the regulation of programmed cell death in immature proliferative otic neuroblasts remains poorly understood. The protein kinase AKT acts as a node, playing a critical role in controlling cell survival and cell cycle progression. AKT is activated by trophic factors, including insulin-like growth factor I (IGF-I), through the generation of the lipidic second messenger phosphatidylinositol 3-phosphate by phosphatidylinositol 3-kinase (PI3K). Here we have investigated the role of IGF-dependent activation of the PI3K-AKT pathway in maintenance of otic neuroblasts. By using a combination of organotypic cultures of chicken (Gallus gallus) otic vesicles and acoustic-vestibular ganglia, Western blotting, immunohistochemistry and in situ hybridization, we show that IGF-I-activation of AKT protects neural progenitors from programmed cell death. IGF-I maintains otic neuroblasts in an undifferentiated and proliferative state, which is characterised by the upregulation of the forkhead box M1 (FoxM1) transcription factor. By contrast, our results indicate that post-mitotic p27Kip-positive neurons become IGF-I independent as they extend their neuronal processes. Neurons gradually reduce their expression of the Igf1r, while they increase that of the neurotrophin receptor, TrkC. Proliferative otic neuroblasts are dependent on the activation of the PI3K-AKT pathway by IGF-I for survival during the otic neuronal progenitor phase of early inner ear development.
登录
查看更多内容
影响因子：
3.4
作者：
Cediel, R;Riquelme, R;Varela-Nieto, I
通讯作者：
Varela-Nieto, I
影响因子：
2.7
作者：
AVILA, MA;VARELANIETO, I;REPRESA, J
通讯作者：
REPRESA, J
影响因子：
10.5
作者：
Chen, WS;Xu, PZ;Hay, N
通讯作者：
Hay, N
影响因子：
2.5
作者：
Davies, Dawn
通讯作者：
Davies, Dawn
DOI：
10.1007/bf01744256
发表时间：
1991-01-01
期刊：
ANATOMY AND EMBRYOLOGY
影响因子：
--
作者：
HEMOND, SG;MOREST, DK
通讯作者：
MOREST, DK