Department of Biology, University of Rochester, River Campus Box 270211, Rochester, NY 14627, USA.
Development. 2011 Mar;138(6):1045-55. doi: 10.1242/dev.056671. Epub 2011 Feb 9.
Precise control of somatic stem cell proliferation is crucial to ensure maintenance of tissue homeostasis in high-turnover tissues. In Drosophila, intestinal stem cells (ISCs) are essential for homeostatic turnover of the intestinal epithelium and ensure epithelial regeneration after tissue damage. To accommodate these functions, ISC proliferation is regulated dynamically by various growth factors and stress signaling pathways. How these signals are integrated is poorly understood. Here, we show that EGF receptor signaling is required to maintain the proliferative capacity of ISCs. The EGF ligand Vein is expressed in the muscle surrounding the intestinal epithelium, providing a permissive signal for ISC proliferation. We find that the AP-1 transcription factor FOS serves as a convergence point for this signal and for the Jun N-terminal kinase (JNK) pathway, which promotes ISC proliferation in response to stress. Our results support the notion that the visceral muscle serves as a functional 'niche' for ISCs, and identify FOS as a central integrator of a niche-derived permissive signal with stress-induced instructive signals, adjusting ISC proliferation to environmental conditions.
精确控制体干细胞增殖对于确保高周转率组织中的组织稳态至关重要。在果蝇中，肠干细胞（ISCs）对于肠上皮的稳态更新以及组织损伤后的上皮再生是必不可少的。为了适应这些功能，ISC 的增殖受到各种生长因子和应激信号通路的动态调节。这些信号是如何整合的还知之甚少。在这里，我们表明 EGF 受体信号对于维持 ISC 的增殖能力是必需的。EGF 配体 Vein 在肠上皮周围的肌肉中表达，为 ISC 增殖提供了一个许可信号。我们发现，AP-1 转录因子 FOS 作为该信号和 Jun N-末端激酶（JNK）途径的汇聚点，促进 ISC 增殖以应对应激。我们的结果支持这样一种观点，即内脏肌肉作为 ISC 的功能性“龛位”，并确定 FOS 作为龛位衍生的许可信号与应激诱导的指令信号的中央整合因子，根据环境条件调节 ISC 增殖。
