Aradhya Rajaguru, Zmojdzian Monika, Da Ponte Jean Philippe, Jagla Krzysztof
Génétique Reproduction et Développement, INSERM U1103, CNRS UMR6293, Clermont-Ferrand, France.
Elife. 2015 Dec 9;4:e08497. doi: 10.7554/eLife.08497.
How stem cells specified during development keep their non-differentiated quiescent state, and how they are reactivated, remain poorly understood. Here, we applied a Drosophila model to follow in vivo behavior of adult muscle precursors (AMPs), the transient fruit fly muscle stem cells. We report that emerging AMPs send out thin filopodia that make contact with neighboring muscles. AMPs keep their filopodia-based association with muscles throughout their dormant state but also when they start to proliferate, suggesting that muscles could play a role in AMP reactivation. Indeed, our genetic analyses indicate that muscles send inductive dIlp6 signals that switch the Insulin pathway ON in closely associated AMPs. This leads to the activation of Notch, which regulates AMP proliferation via dMyc. Altogether, we report that Drosophila AMPs display homing behavior to muscle niche and that the niche-driven Insulin-Notch-dMyc cascade plays a key role in setting the activated state of AMPs.
在发育过程中，干细胞是如何维持其未分化的静止状态以及如何被重新激活的，目前仍知之甚少。在此，我们应用果蝇模型来追踪成年肌肉前体细胞（AMPs）的体内行为，AMPs是果蝇短暂存在的肌肉干细胞。我们报告称，新出现的AMPs会伸出细的丝状伪足与邻近肌肉接触。AMPs在整个休眠状态以及开始增殖时，都通过丝状伪足与肌肉保持联系，这表明肌肉可能在AMPs重新激活中发挥作用。事实上，我们的基因分析表明，肌肉会发出诱导性的dIlp6信号，该信号会开启紧密相连的AMPs中的胰岛素信号通路。这会导致Notch激活，Notch通过dMyc调节AMPs的增殖。总之，我们报告称果蝇AMPs表现出归巢至肌肉微环境的行为，并且微环境驱动的胰岛素-Notch-dMyc级联反应在设定AMPs的激活状态中起关键作用。
