Department of Biology, McGill University, 1205 Doctor Penfield Avenue, Montréal, QC H3A 1B1, Canada.
Cell Rep. 2013 Aug 29;4(4):791-802. doi: 10.1016/j.celrep.2013.07.038. Epub 2013 Aug 22.
Spatially restricted epidermal growth factor receptor (EGFR) activity plays a central role in patterning the follicular epithelium of the Drosophila ovary. In midoogenesis, localized EGFR activation is achieved by the graded dorsal anterior localization of its ligand, Gurken. Graded EGFR activity determines multiple dorsal anterior fates along the dorsal-ventral axis but cannot explain the sharp posterior limit of this domain. Here, we show that posterior follicle cells express the T-box transcription factors Midline and H15, which render cells unable to adopt a dorsal anterior fate in response to EGFR activation. The posterior expression of Midline and H15 is itself induced in early oogenesis by posteriorly localized EGFR signaling, defining a feedback loop in which early induction of Mid and H15 confers a molecular memory that fundamentally alters the outcome of later EGFR signaling. Spatial regulation of the EGFR pathway thus occurs both through localization of the ligand and through localized regulation of the cellular response.
表皮生长因子受体 (EGFR) 的空间限制活性在果蝇卵巢滤泡上皮的模式形成中起着核心作用。在中期发生过程中，通过其配体 Gurken 的梯度背侧前部定位来实现局部 EGFR 激活。梯度 EGFR 活性沿背腹轴决定了多个背侧前部命运，但不能解释该区域的尖锐后缘。在这里，我们表明，后滤泡细胞表达 T 盒转录因子 Midline 和 H15，这使得细胞无法对 EGFR 激活产生的背侧前部命运作出反应。早期卵发生中 Midline 和 H15 的后表达本身是由后部定位的 EGFR 信号诱导的，这定义了一个反馈回路，其中 Mid 和 H15 的早期诱导赋予了分子记忆，从根本上改变了后期 EGFR 信号的结果。因此，EGFR 途径的空间调节既通过配体的定位，也通过细胞反应的局部调节来发生。
