Foxo3 is a PI3K-dependent molecular switch controlling the initiation of oocyte growth
Foxo3 is a PI3K-dependent molecular switch controlling the initiation of oocyte growth
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DOI：
10.1016/j.ydbio.2008.06.017
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发表时间：
2008-09-01
影响因子：
2.7
通讯作者：
Castrillon, Diego H.
中科院分区：
文献类型：
--
作者：
John, George B.;Gallardo, Teresa D.;Castrillon, Diego H.
在哺乳动物中，卵母细胞被包装成紧凑的结构-原始卵泡-在长时间间隔内保持惰性，直到单个卵泡通过称为原始卵泡激活的过程恢复生长。在这里，我们表明，磷酸肌醇3-激酶（PI 3 K）信号通路控制原始卵泡激活通过叉头转录因子Foxo 3。在卵母细胞内，Foxo 3受到核质穿梭的调节。Foxo 3在原始卵泡组装期间输入到细胞核中，并在激活时输出。卵母细胞特异性的Pten消融导致PI 3 K诱导的Akt活化、Foxo 3过度磷酸化和Foxo 3核输出，从而使原始卵泡活化，定义了PI 3 K通路和Foxo 3控制这一过程的步骤。在成年卵母细胞中使用一种新的生殖系遗传分析工具Vasa-Cre（ERT 2）诱导Pten和Foxo 3的消融，表明该途径在整个生命过程中发挥作用。因此，PI 3 K途径的主要生理作用是通过Foxo 3控制原始卵泡激活。(C)2008年爱思唯尔公司All rights reserved.
In mammals, oocytes are packaged into compact structures-primordial follicles-which remain inert for prolonged intervals until individual follicles resume growth via a process known as primordial follicle activation. Here we show that the phosphoinositide 3-kinase (PI3K) signalling pathway controls primordial follicle activation through the forkhead transcription factor Foxo3. Within oocytes, Foxo3 is regulated by nucleocytoplasmic shuttling. Foxo3 is imported into the nucleus during primordial follicle assembly, and is exported Upon activation. Oocyte-specific ablation of Pten resulted in PI3K-induced Akt activation, Foxo3 hyperphosphorylation, and Foxo3 nuclear export, thereby trigggering primordial follicle activation, defining the steps by which the PI3K pathway and Foxo3 control this process. Inducible ablation of Pten and Foxo3 in adult oocytes using a new tool for genetic analysis of the germline, Vasa-Cre(ERT2), showed that this pathway functions throughout life. Thus, a principal physiologic role of the PI3K pathway is to control primordial follicle activation via Foxo3. (C) 2008 Elsevier Inc. All rights reserved.