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 towards 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 have 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）子代的分化。本研究鉴定出两种蛋白——Six4与Groucho（Gro），二者可衔接两条通路的活性，进而调控FSC谱系中最早的细胞命运决定事件。研究数据显示，Six4与Gro可通过增强Notch通路活性，推动细胞向极细胞命运分化。EGFR信号通路会拮抗Gro的这一功能：其通过磷酸化细胞外调节蛋白激酶（p-ERK）介导的磷酸化修饰，抑制Gro依赖的转录抑制作用。本研究还发现，磷酸化形式的Gro会在新形成的pFC中持续存留，这可能会延迟细胞分化，并为这些细胞提供一段临时的EGFR信号记忆。综上，这些研究结果证实，磷酸化Gro可作为FSC谱系中过渡态的标志物，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串扰。