Basolateral junctions are sufficient to suppress epithelial invasion during Drosophila oogenesis

Abstract

Epithelial junctions play crucial roles during metazoan evolution and development by facilitating tissue formation, maintenance, and function. Little is known about the role of distinct types of junctions in controlling epithelial transformations leading to invasion of neighboring tissues. Discovering the key junction complexes that control these processes and how they function may also provide mechanistic insight into carcinoma cell invasion. Here, using the Drosophila ovary as a model, we show that four proteins of the basolateral junction (BLJ), Fasciclin-2, Neuroglian, Discs-large, and Lethal-giant-larvae, but not proteins of other epithelial junctions, directly suppress epithelial tumorigenesis and invasion. Remarkably, the expression pattern of Fasciclin-2 predicts which cells will invade. We compared the apicobasal polarity of BLJ tumor cells to border cells (BCs), an epithelium-derived cluster that normally migrates during mid-oogenesis. Both tumor cells and BCs differentiate a lateralized membrane pattern that is necessary but not sufficient for invasion. Independent of lateralization, derepression of motility pathways is also necessary, as indicated by a strong linear correlation between faster BC migration and an increased incidence of tumor invasion. However, without membrane lateralization, derepression of motility pathways is also not sufficient for invasion. Our results demonstrate that spatiotemporal patterns of basolateral junction activity directly suppress epithelial invasion by organizing the cooperative activity of distinct polarity and motility pathways. Developmental Dynamics 236:364 -373, 2007.

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

“…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.…”

“…10,18,19,[22][23][24][25][26] We and others have shown that lgl/dlg/scrib are required for a number of developmental controls during oogenesis. 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.…”

Basolateral Junctions Utilize Warts Signaling to Control Epithelial-Mesenchymal Transition and Proliferation Crucial For Migration and Invasion of Drosophila Ovarian Epithelial Cells

“…A universal theme is that each type of epithelial junction is organized by a transmembrane receptor bound to a cytoplasmic scaffolding protein, thus enabling assembly of a supermolecular complex of proteins within the cellular cortex at sites of intercellular contact (Knust 2002). Epithelial junctions are relatively stable in stationary epithelia, but they undergo extensive remodeling when epithelia transform into migratory cells during embryonic development, tissue repair and regeneration, and pathological conditions such as cancer (Grunert et al 2003;Shook and Keller 2003;Szafranski and Goode 2004;Larue and Bellacosa 2005;Thiery and Sleeman 2006;Szafranski and Goode 2007). Understanding how epithelial junctions are used for epithelial maintenance and epithelial remodeling during normal development may allow targeting tumor invasion without perturbing normal tissue homeostasis.…”

“…Once follicle cell proliferation ceases, differentiation begins, setting the stage for two migration events during midoogenesis. A small cluster of cells that reside in the anterior epithelium, called border cells (BC), undergo a partial epithelial-mesenchymal transition (EMT), break free from adjacent epithelial cells, and migrate posterior between the nurse cells to the oocyte (Figure 2A) (Niewiatomska et al 1999;Starz-Gaiano and Montell 2004;Szafranski and Goode 2007). At the same time, most follicle cells that surround the nurse cells move posterior to encapsulate the oocyte (Goode et al 2005).…”

“…At the same time, most follicle cells that surround the nurse cells move posterior to encapsulate the oocyte (Goode et al 2005). 1 Each cell within the follicular epithelium has five junctions (Tanentzapf et al 2000;Szafranski and Goode 2007). An apical junction connects to the germ line, while a basal junction connects to the basement membrane that surrounds each egg chamber.…”