Insulin signaling promotes germline proliferation in C. elegans
Insulin signaling promotes germline proliferation in C. elegans
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DOI：
10.1242/dev.042523
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发表时间：
2010-02-15
期刊：
影响因子：
4.6
通讯作者：
Hubbard, E. Jane Albert
中科院分区：
文献类型：
--
作者：
Michaelson, David;Korta, Dorota Z.;Hubbard, E. Jane Albert
在发育过程中，细胞增殖必须与细胞命运规范相协调，但控制这两个关键发育方面的途径之间的相互作用尚不清楚。在早期生殖系发育过程中，细胞命运指定和增殖的协调尤其重要，因为它影响干细胞/祖细胞种群的建立，并最终影响配子的产生。在线虫中，胰岛素/IGF样受体(IIR)信号与生育有关，但生育缺陷的基础尚未得到表征。我们发现，IIR信号对幼虫生殖系的强大增殖是必需的，与它在阻止Dauer进入方面的作用是分开的。IIR信号刺激幼虫生殖系细胞周期。这种活动不同于Notch信号，以一种主要的生殖系自主方式发生，并对编码假定的胰岛素样配体的INS-3和INS-33的体细胞活动做出反应。IIR信号在这一作用中通过典型的PI3K途径发挥作用，抑制DAF-16/FOXO。然而，来自这些配体的信号并不抑制神经元和肠道中的daf-16，这两个组织之前参与了其他IIR角色。我们的数据与模型一致，在该模型中：(1)在充分的繁殖条件下，幼虫生殖系对胰岛素信号做出反应，以确保生殖系强劲的增殖，从而建立生殖系干细胞种群；(2)不同的胰岛素样配体通过作用于不同组织中的IIR信号而促进不同的表型。
Cell proliferation must be coordinated with cell fate specification during development, yet interactions among pathways that control these two critical aspects of development are not well understood. The coordination of cell fate specification and proliferation is particularly crucial during early germline development, when it impacts the establishment of stem/progenitor cell populations and ultimately the production of gametes. In C. elegans, insulin/IGF-like receptor (IIR) signaling has been implicated in fertility, but the basis for the fertility defect had not been previously characterized. We found that IIR signaling is required for robust larval germline proliferation, separate from its well-characterized role in preventing dauer entry. IIR signaling stimulates the larval germline cell cycle. This activity is distinct from Notch signaling, occurs in a predominantly germline-autonomous manner, and responds to somatic activity of ins-3 and ins-33, genes that encode putative insulin-like ligands. IIR signaling in this role acts through the canonical PI3K pathway, inhibiting DAF-16/FOXO. However, signaling from these ligands does not inhibit daf-16 in neurons nor in the intestine, two tissues previously implicated in other IIR roles. Our data are consistent with a model in which: (1) under replete reproductive conditions, the larval germline responds to insulin signaling to ensure robust germline proliferation that builds up the germline stem cell population; and (2) distinct insulin-like ligands contribute to different phenotypes by acting on IIR signaling in different tissues.