Gujar Mahekta R, Gao Yang, Teng Xiang, Deng Qiannan, Lin Kun-Yang, Tan Ye Sing, Toyama Yusuke, Wang Hongyan
Neuroscience & Behavioral Disorders Programme, Duke-NUS Medical School, 8 College Road, Singapore 169857, Singapore.
Mechanobiology Institute, Level 5, T-lab Building, 5A Engineering Drive 1, Singapore 117411, Singapore.
Dev Cell. 2023 Oct 9;58(19):1933-1949.e5. doi: 10.1016/j.devcel.2023.07.010. Epub 2023 Aug 10.
The ability of stem cells to switch between quiescent and proliferative states is crucial for maintaining tissue homeostasis and regeneration. In Drosophila, quiescent neural stem cells (qNSCs) extend a primary protrusion, a hallmark of qNSCs. Here, we have found that qNSC protrusions can be regenerated upon injury. This regeneration process relies on the Golgi apparatus that acts as the major acentrosomal microtubule-organizing center in qNSCs. A Golgi-resident GTPase Arf1 and its guanine nucleotide exchange factor Sec71 promote NSC reactivation and regeneration via the regulation of microtubule growth. Arf1 physically associates with its new effector mini spindles (Msps)/XMAP215, a microtubule polymerase. Finally, Arf1 functions upstream of Msps to target the cell adhesion molecule E-cadherin to NSC-neuropil contact sites during NSC reactivation. Our findings have established Drosophila qNSCs as a regeneration model and identified Arf1/Sec71-Msps pathway in the regulation of microtubule growth and NSC reactivation.
干细胞在静止状态和增殖状态之间转换的能力对于维持组织稳态和再生至关重要。在果蝇中,静止神经干细胞(qNSCs)会伸出一个初级突起,这是qNSCs的一个标志。在这里,我们发现qNSC突起在损伤后能够再生。这个再生过程依赖于高尔基体,高尔基体在qNSCs中作为主要的无中心体微管组织中心发挥作用。一种驻留在高尔基体的GTP酶Arf1及其鸟嘌呤核苷酸交换因子Sec71通过调节微管生长来促进神经干细胞的重新激活和再生。Arf1与它的新效应器微型纺锤体(Msps)/XMAP215(一种微管聚合酶)发生物理结合。最后,Arf1在Msps的上游发挥作用,在神经干细胞重新激活过程中将细胞粘附分子E-钙粘蛋白靶向到神经干细胞-神经纤维接触位点。我们的研究结果将果蝇qNSCs确立为一种再生模型,并确定了Arf1/Sec71-Msps途径在微管生长和神经干细胞重新激活的调节中的作用。