Role of Scrib and Dlg in anterior-posterior patterning of the follicular epithelium during Drosophila oogenesis

Abstract

BackgroundProper 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.ResultsWe 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.ConclusionIn 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.

Requirements of Lgl in cell differentiation and motility during Drosophila ovarian follicular epithelium morphogenesis

“…10,[18][19][20]22,23,[27][28][29][30][31][32][33][34][35][36] In particular, we have identified Lgl as an essential regulator in PFC specification and differentiation, and a role of dlg/scrib in both anterior and posterior patterning of the follicular epithelium. 32,37 In this paper, we show that lgl genetically interacts with dlg/scrib in PFC fate induction, suggesting a common regulatory pathway in this process. Meanwhile, we present evidence that lgl functions in subdivision of anterior follicle cells into functionally distinct subpopulations and control of the collective border cell migration at mid-oogenesis.…”

“…Ovary dissections and antibody staining were performed as described previously. 37 The following primary antibodies were used in this work: mouse anti-β-gal (1:10 DSHB 40-1a), rat anti-Slbo (1:500 gift from P Rørth), 60 rabbit anti-aPKC (1:500 Santa Cruz), mouse anti-Arm (1:200 DSHB N2 7A1), rat anti-DE-cad (1:10 DSHB DCAD2), mouse anti-Hnt (1:200 DSHB 1G9), rabbit anti-STAT92E (1:1,000 gift from SX Hou), 61 rabbit anti-DG (1:3,000 gift from WM Deng). 62 Secondary antibodies conjugated with Alexa Fluor 488, 546 (Molecular Probes) were used at 1:1,000 dilutions.…”

“…We have shown that mutations in dlg/ scrib cause aberrant anterior patterning of the follicular epithelium. 37 This prompted us to investigate putative role of lgl in this process. Firstly, we tested how loss of lgl function affects induction of border cell, the most terminal anterior fate.…”

“…Although the common regulatory pathway appears complex, our findings suggest that defects in coordinated activation of JAK, Notch and EGFR signaling pathways may causally link loss of lgl/dlg/scrib to all mutant clones covering both stretched and centripetal cells (lgl 4 : n = 8). Considering that the STAT92E nuclear accumulation indicative of JAK signaling activity can be detected in the specified squamous FCs surrounding the nurse cells, but not in specified centripetal cells at the wild-type stage 10 egg chambers, 37 we only tested the mutant stretched cell population for JAK signaling activity pattern. As expected, we observed that STAT92E protein accumulates in nuclei of the stretched cells lacking lgl function to a level comparable with that in the wildtype ones (lgl 4 : n = 25, lgl 4w3 : n = 19 and data not shown), suggesting the presence of activated JAK signaling.…”

“…32 Most recently, we showed that scrib genetically interacts with dlg in posterior patterning of ovarian follicular epithelium. 37 Considering that lgl, dlg and scrib work in concert to regulate cell polarity and proliferation in the epithelial tissues, 10,18,19,22,23,[38][39][40][41][42] we intended to determine whether these three genes act in a common pathway to function in PFC specification and differentiation. To address this issue, we tested for genetic interactions among the three mutations and detected strong interactions of lgl with dlg and scrib in the examined process.…”