Data from: Phosphorylated Groucho delays differentiation in the follicle stem cell lineage by providing a molecular memory of EGFR signaling in the niche

In the epithelial follicle stem cells (FSCs) of the Drosophila ovary, Epidermal Growth Factor Receptor (EGFR) signaling promotes self-renewal whereas Notch signaling promotes differentiation of the prefollicle cell (pFC) daughters. We have identified two proteins, Six4 and Groucho (Gro), that link the activity of these two pathways to regulate the earliest cell fate decision in the FSC lineage. Our data indicate that Six4 and Gro promote differentiation toward the polar cell fate by promoting Notch pathway activity. This activity of Gro is antagonized by EGFR signaling, which inhibits Gro-dependent repression via p-ERK mediated phosphorylation. We found that the phosphorylated form of Gro persists in newly formed pFCs, which may delay differentiation and provide these cells with a temporary memory of the EGFR signal. Collectively, these findings demonstrate that phosphorylated Gro labels a transition state in the FSC lineage and describe the interplay between Notch and EGFR signaling that governs the differentiation processes during this period.

在果蝇卵巢的上皮卵泡干细胞（epithelial follicle stem cells, FSCs）中，表皮生长因子受体（Epidermal Growth Factor Receptor, EGFR）信号通路可促进干细胞自我更新，而Notch信号通路则促进前卵泡细胞（prefollicle cell, pFC）子代细胞的分化。我们已鉴定出两种蛋白——Six4与Groucho（Gro），它们可连接上述两条信号通路的活性，以调控FSC谱系中最早的细胞命运决定事件。我们的实验数据表明，Six4与Gro可通过增强Notch通路活性，促进细胞向极细胞命运方向分化。EGFR信号通路可通过p-ERK介导的磷酸化作用抑制Gro依赖的基因抑制，从而拮抗Gro的上述活性。我们发现，磷酸化形式的Gro在新生成的前卵泡细胞中持续存在，这或许可延迟细胞分化，并为这些细胞提供对EGFR信号的暂时性记忆。综上，这些研究结果证实，磷酸化的Gro可作为FSC谱系中过渡状态的标记分子，并阐明了调控此阶段分化过程的Notch与EGFR信号通路之间的相互调控机制。