Li Qi, Shen Ling, Xin Tianchi, Xiang Wenjuan, Chen Wenlian, Gao Yin, Zhu Mingwei, Yu Lingzhu, Li Mingfa
MoE Key Laboratory of Developmental Genetics and Neuropsychiatric Diseases, Bio-X Center, School of Life Science and Biotechnology, Shanghai Jiao Tong University, 200240 Shanghai, PR
BMC Dev Biol. 2009 Dec 1;9:60. doi: 10.1186/1471-213X-9-60.
Proper patterning of the follicle cell epithelium over the egg chamber is essential for the Drosophila egg development. Differentiation of the epithelium into several distinct cell types along the anterior-posterior axis requires coordinated activities of multiple signaling pathways. Previously, we reported that lethal(2)giant larvae (lgl), a Drosophila tumor suppressor gene, is required in the follicle cells for the posterior follicle cell (PFC) fate induction at mid-oogenesis. Here we explore the role of another two tumor suppressor genes, scribble (scrib) and discs large (dlg), in the epithelial patterning.
We found that removal of scrib or dlg function from the follicle cells at posterior terminal of the egg chamber causes a complete loss of the PFC fate. Aberrant specification and differentiation of the PFCs in the mosaic clones can be ascribed to defects in coordinated activation of the EGFR, JAK and Notch signaling pathways in the multilayered cells. Meanwhile, the clonal analysis revealed that loss-of-function mutations in scrib/dlg at the anterior domains result in a partially penetrant phenotype of defective induction of the stretched and centripetal cell fate, whereas specification of the border cell fate can still occur in the most anterior region of the mutant clones. Further, we showed that scrib genetically interacts with dlg in regulating posterior patterning of the epithelium.
In this study we provide evidence that scrib and dlg function differentially in anterior and posterior patterning of the follicular epithelium at oogenesis. Further genetic analysis indicates that scrib and dlg act in a common pathway to regulate PFC fate induction. This study may open another window for elucidating role of scrib/dlg in controlling epithelial polarity and cell proliferation during development.
卵泡细胞上皮在卵室上的正确模式形成对于果蝇卵子发育至关重要。上皮细胞沿前后轴分化为几种不同的细胞类型需要多种信号通路的协同活动。此前，我们报道了致死（2）巨幼虫（lgl），一种果蝇肿瘤抑制基因，在卵泡细胞中是卵子发生中期诱导后卵泡细胞（PFC）命运所必需的。在这里，我们探讨另外两个肿瘤抑制基因，scribble（scrib）和盘大（dlg），在上皮模式形成中的作用。
我们发现从卵室后端的卵泡细胞中去除scrib或dlg功能会导致PFC命运完全丧失。镶嵌克隆中PFC的异常特化和分化可归因于多层细胞中EGFR、JAK和Notch信号通路协同激活的缺陷。同时，克隆分析表明，scrib/dlg在前部区域的功能丧失突变导致拉伸和向心细胞命运诱导缺陷的部分穿透表型，而边界细胞命运的特化仍可在突变克隆的最前部区域发生。此外，我们表明scrib在调节上皮细胞的后部模式形成中与dlg发生遗传相互作用。
在本研究中，我们提供证据表明scrib和dlg在卵子发生过程中卵泡上皮细胞的前后模式形成中发挥不同作用。进一步的遗传分析表明，scrib和dlg在共同途径中发挥作用以调节PFC命运诱导。这项研究可能为阐明scrib/dlg在发育过程中控制上皮极性和细胞增殖的作用打开另一扇窗口。
