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（FSCs）中，表皮生长因子受体（EGFR）信号通路可促进细胞自我更新，而Notch信号通路则推动前卵泡细胞（pFC）子代细胞的分化。本研究鉴定出Six4与Groucho（Gro）两种蛋白，二者可通过调控上述两条信号通路的活性，对FSC谱系中最早期的细胞命运决定发挥调节作用。实验数据表明，Six4与Gro可通过增强Notch信号通路的活性，促进细胞向极细胞命运方向分化。EGFR信号通路会拮抗Gro的这一功能，其通过p-ERK介导的磷酸化过程，抑制Gro依赖的基因阻遏作用。研究发现，磷酸化形式的Gro会在新生成的pFC中持续存留，这或许能够延缓细胞分化，并为这些细胞赋予一段短暂的EGFR信号记忆。综上，本研究结果证实，磷酸化Gro可作为FSC谱系中过渡状态的标志物，并阐明了调控该时期分化过程的Notch与EGFR信号通路之间的相互作用机制。