秀丽隐杆线虫的DAF-18/PTEN介导生殖系中细胞周期和生长的营养依赖性停滞。

C. elegans DAF-18/PTEN mediates nutrient-dependent arrest of cell cycle and growth in the germline.

作者信息

Fukuyama Masamitsu, Rougvie Ann E, Rothman Joel H

机构信息

Department of Molecular, Cellular and Developmental Biology, University of California, Santa Barbara, 93106, USA.

出版信息

Curr Biol. 2006 Apr 18;16(8):773-9. doi: 10.1016/j.cub.2006.02.073.

DOI:10.1016/j.cub.2006.02.073

PMID:16631584

Abstract

The molecular pathways that link nutritional cues to developmental programs are poorly understood. Caenorhabditis elegans hatchlings arrest in a dormant state termed "L1 diapause" until food is supplied. However, little is known about what signal transduction pathways mediate nutritional status to control arrest and initiation of postembryonic development. We report that C. elegans embryonic germline precursors undergo G2 arrest with condensed chromosomes and remain arrested throughout L1 diapause. Loss of the DAF-18/PTEN tumor suppressor bypasses this arrest, resulting in inappropriate germline growth dependent on the AGE-1/PI-3 and AKT-1/PKB kinases. DAF-18 also regulates an insulin/IGF-like pathway essential for longevity and dauer larva formation. However, DAF-16/FoxO, which is repressed by this pathway, is not required for germline arrest in L1 diapause. Thus, these findings indicate that quiescence of germline development during L1 diapause is not a passive consequence of nutrient deprivation, but rather is actively maintained by DAF-18 through a pathway distinct from that which regulates longevity and dauer formation.

摘要

将营养信号与发育程序联系起来的分子途径目前还知之甚少。秀丽隐杆线虫的幼虫会进入一种称为“L1滞育”的休眠状态，直到有食物供应才会解除。然而，对于何种信号转导途径介导营养状态以控制胚胎后发育的停滞和启动，我们却知之甚少。我们发现，秀丽隐杆线虫的胚胎生殖系前体细胞会经历带有浓缩染色体的G2期停滞，并在整个L1滞育期持续停滞。DAF-18/PTEN肿瘤抑制因子的缺失绕过了这种停滞，导致了依赖于AGE-1/PI-3和AKT-1/PKB激酶的不适当的生殖系生长。DAF-18还调节一条对寿命和 dauer幼虫形成至关重要的胰岛素/胰岛素样生长因子信号通路。然而，被该信号通路抑制的DAF-16/FoxO对于L1滞育期生殖系的停滞并非必需。因此，这些发现表明，L1滞育期生殖系发育的静止并非营养剥夺的被动结果，而是由DAF-18通过一条不同于调节寿命和 dauer形成的信号通路主动维持的。