Abstract
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.
Highlights
Adult stem cell divisions produce asymmetric outcomes such that one daughter self-renews while the other goes on to differentiate
As follicle stem cell (FSC) can be unambiguously identified as the anterior-most cell in an FSC clone induced in adult flies by mitotic recombination, we generated FSC clones marked by the absence of green florescent protein (GFP) and stained for phosphorylated extracellular signal-related kinase (pErk)
To determine whether this pErk signal is dependent upon epidermal growth factor receptor (EGFR), we generated FSC clones that are homozygous for Egfrf24, a loss-of-function allele, and stained for pErk
Summary
Adult stem cell divisions produce asymmetric outcomes such that one daughter self-renews while the other goes on to differentiate. In many stem cell lineages, the non-stem cell daughter initially has the potential to re-enter the niche and become a stem cell, indicating that it does not immediately commit to the fully differentiated fate (Morrison and Spradling, 2008; Simons and Clevers, 2011). Previous studies have exploited visible differences in the cellular and sub-cellular morphology of stem cells and their daughters to investigate the signals that govern the segregation of cell fates (Xie and Spradling, 1998; Lim et al, 2000; Kiger et al, 2001; Ohlstein and Spradling, 2007; Yin et al, 2013). Signals that regulate the development of cell polarity may play an important role in the segregation of epithelial stem cell and daughter cell fates. The relationship between cell polarity and differentiation in epithelial stem cell lineages is poorly understood
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