Department of Genetics, Washington University School of Medicine, St Louis, MO 63110, USA.
Dev Cell. 2011 May 17;20(5):677-88. doi: 10.1016/j.devcel.2011.04.009.
Tissues that generate specialized cell types in a production line must coordinate developmental mechanisms with physiological demand, although how this occurs is largely unknown. In the Caenorhabditis elegans hermaphrodite, the developmental sex-determination cascade specifies gamete sex in the distal germline, while physiological sperm signaling activates MPK-1/ERK in the proximal germline to control plasma membrane biogenesis and organization during oogenesis. We discovered repeated utilization of a self-contained negative regulatory module, consisting of NOS-3 translational repressor, FEM-CUL-2 (E3 ubiquitin ligase), and TRA-1 (Gli transcriptional repressor), which acts both in sex determination and in physiological demand control of oogenesis, coordinating these processes. In the distal germline, where MPK-1 is not activated, TRA-1 represses the male fate as NOS-3 functions in translational repression leading to inactivation of the FEM-CUL-2 ubiquitin ligase. In the proximal germline, sperm-dependent physiological MPK-1 activation results in phosphorylation-based inactivation of NOS-3, FEM-CUL-2-mediated degradation of TRA-1 and the promotion of membrane organization during oogenesis.
组织在流水线中产生特化的细胞类型，必须协调发育机制与生理需求，尽管这是如何发生的在很大程度上仍是未知的。在秀丽隐杆线虫雌雄同体中，发育性别决定级联在远端生殖系中指定配子性别，而生理精子信号激活近端生殖系中的 MPK-1/ERK，以在卵子发生过程中控制质膜发生和组织。我们发现了自我包含的负反馈调节模块的重复利用，该模块由 NOS-3 翻译抑制剂、FEM-CUL-2（E3 泛素连接酶）和 TRA-1（Gli 转录抑制剂）组成，该模块在性别决定和卵子发生的生理需求控制中都起作用，协调这些过程。在 MPK-1 未被激活的远端生殖系中，TRA-1 抑制雄性命运，因为 NOS-3 在翻译抑制中起作用，导致 FEM-CUL-2 泛素连接酶失活。在近端生殖系中，精子依赖性的生理 MPK-1 激活导致基于磷酸化的 NOS-3 失活、FEM-CUL-2 介导的 TRA-1 降解以及卵子发生过程中质膜组织的促进。
