Romani Patrizia, Bernardi Fabio, Hackney Jennifer, Dobens Leonard, Gargiulo Giuseppe, Cavaliere Valeria
School of Biological Sciences, University of Missouri, Kansas City, Missouri 64110, USA.
Genetics. 2009 Jan;181(1):165-75. doi: 10.1534/genetics.108.096008. Epub 2008 Nov 17.
Proper assembly and maintenance of epithelia are critical for normal development and homeostasis. Here, using the Drosophila ovary as a model, we identify a role for the B1 isoform of the ecdysone receptor (EcR-B1) in this process. We performed a reverse genetic analysis of EcR-B1 function during oogenesis and demonstrate that silencing of this receptor isoform causes loss of integrity and multilayering of the follicular epithelium. We show that multilayered follicle cells lack proper cell polarity with altered distribution of apical and basolateral cell polarity markers including atypical-protein kinase C (aPKC), Discs-large (Dlg), and Scribble (Scrib) and aberrant accumulation of adherens junctions and F-actin cytoskeleton. We find that the EcR-B1 isoform is required for proper follicle cell polarity both during early stages of oogenesis, when follicle cells undergo the mitotic cell cycle, and at midoogenesis when these cells stop dividing and undergo several endocycles. In addition, we show that the EcR-B1 isoform is required during early oogenesis for follicle cell survival and that disruption of its function causes apoptotic cell death induced by caspase.
上皮细胞的正确组装和维持对于正常发育和体内平衡至关重要。在此,我们以果蝇卵巢为模型,确定了蜕皮激素受体(EcR - B1)的B1亚型在此过程中的作用。我们对卵子发生过程中EcR - B1的功能进行了反向遗传学分析,结果表明该受体亚型的沉默会导致卵泡上皮完整性丧失和多层化。我们发现多层卵泡细胞缺乏正常的细胞极性,顶端和基底外侧细胞极性标记物(包括非典型蛋白激酶C(aPKC)、盘状大蛋白(Dlg)和scribble(Scrib))的分布发生改变,黏着连接和F - 肌动蛋白细胞骨架异常积累。我们发现,在卵子发生的早期阶段,即卵泡细胞经历有丝分裂细胞周期时,以及在卵子发生中期,即这些细胞停止分裂并经历几次内复制周期时,EcR - B1亚型对于卵泡细胞的正常极性都是必需的。此外,我们表明在卵子发生早期,EcR - B1亚型对于卵泡细胞的存活是必需的,其功能的破坏会导致由半胱天冬酶诱导的凋亡细胞死亡。