Castanieto Angela, Johnston Michael J, Nystul Todd G
Department of Anatomy, University of California, San Francisco, San Francisco, United States.
Elife. 2014 Dec 1;3:e04437. doi: 10.7554/eLife.04437.
Epithelial stem cells divide asymmetrically, such that one daughter replenishes the stem cell pool and the other differentiates. We found that, in the epithelial follicle stem cell (FSC) lineage of the Drosophila ovary, epidermal growth factor receptor (EGFR) signaling functions specifically in the FSCs to promote the unique partially polarized state of the FSC, establish apical-basal polarity throughout the lineage, and promote FSC maintenance in the niche. In addition, we identified a novel connection between EGFR signaling and the cell-polarity regulator liver kinase B1 (LKB1), which indicates that EGFR signals through both the Ras-Raf-MEK-Erk pathway and through the LKB1-AMPK pathway to suppress apical identity. The development of apical-basal polarity is the earliest visible difference between FSCs and their daughters, and our findings demonstrate that the EGFR-mediated regulation of apical-basal polarity is essential for the segregation of stem cell and daughter cell fates.
上皮干细胞进行不对称分裂,使得一个子细胞补充干细胞库,另一个子细胞则发生分化。我们发现,在果蝇卵巢的上皮卵泡干细胞(FSC)谱系中,表皮生长因子受体(EGFR)信号传导专门在卵泡干细胞中发挥作用,以促进卵泡干细胞独特的部分极化状态,在整个谱系中建立顶 - 基极性,并促进卵泡干细胞在微环境中的维持。此外,我们确定了EGFR信号传导与细胞极性调节因子肝激酶B1(LKB1)之间的一种新联系,这表明EGFR通过Ras - Raf - MEK - Erk途径以及通过LKB1 - AMPK途径发出信号,以抑制顶端特性。顶 - 基极性的发育是卵泡干细胞与其子代细胞之间最早可见的差异,我们的研究结果表明,EGFR介导的顶 - 基极性调节对于干细胞和子代细胞命运的分离至关重要。