JNK Signaling Controls Border Cell Cluster Integrity and Collective Cell Migration

Abstract

Collective cell movement is a mechanism for invasion identified in many developmental events. Examples include the movement of lateral-line neurons in Zebrafish, cells in the inner blastocyst, and metastasis of epithelial tumors [1]. One key model to study collective migration is the movement of border cell clusters in Drosophila. Drosophila egg chambers contain 15 nurse cells and a single oocyte surrounded by somatic follicle cells. At their anterior end, polar cells recruit several neighboring follicle cells to form the border cell cluster [2]. By stage 9, and over 6 hr, border cells migrate as a cohort between nurse cells toward the oocyte. The specification and directionality of border cell movement are regulated by hormonal and signaling mechanisms [3]. However, how border cells are held together while they migrate is not known. Here, we show that a negative-feedback loop controlling JNK activity regulates border cell cluster integrity. JNK signaling modulates contacts between border cells and between border cells and substratum to sustain collective migration by regulating several effectors including the polarity factor Bazooka and the cytoskeletal adaptor D-Paxillin. We anticipate a role for the JNK pathway in controlling collective cell movements in other morphogenetic and clinical models.

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

“…3L) in the mutant cells respectively. Combined with the previous reports that both aPKC/Bazooka (Baz) complex and DE-Cadherin are required for the collective migration of border cell cluster, 3,6,15,16,44,45 results in this work suggest that Lgl functions in maintaining the cluster integrity through mediating the cell polarity and cell-cell adhesion. To test this, we overexpressed Baz in lgl 4 mutant border cells based on MARCM technique, and observed a significantly reduced penetrance of the dissociated border cell cluster, albeit the phenotype was not fully restored (Fig.…”

“…Overexpression of Baz in lgl mutant cells could partially restore the border cell cluster integrity. Considering that Baz serves as a key mediator in maintaining the cluster integrity during the movement and also acts as a permissive factor for the invasion of tumor cells by stabilizing adhesion between invading follicle cells and the germline cells, 6,16,44 we propose that lgl regulates the collective border cell migration via modulating the cell polarity in a Baz-dependent manner. To test this scenario, we need to design more precise experiments for identifying the putative role of Baz in lgl regulated cell cluster movement.…”

“…3,4 Numerous studies have shown that the collective and guided border cell migration requires a number of coordinated signaling activities such as JAK/STAT, JNK, PVR pathways and ecdysone signaling etc. [5][6][7][8][9][10][11][12][13][14] In addition, the apico-basal polarity and DE-Cadherin based adhesion are crucial for the integrity of border cell cluster during its morphogenetic movement. 6,15,16 As developmental cell migration and pathological cell invasion involve common cellular and biological processes, 3,10,[17][18][19][20][21] further investigation of this model system will contribute to unraveling the molecular mechanisms underlying cancer invasion and metastasis.…”

Modeling and analysis of collective cell migration in an in vivo three-dimensional environment

“…To obtain even smaller clusters, we knocked down E-cadherin specifically in central nonmotile polar cells, which causes clusters to break apart (29). Compared with other methods that generate smaller border cell clusters (34,35), this method does not directly alter the migrating cells themselves, thus presumably minimally changing their properties, and the smaller clusters generated are able to migrate. We measured average speed and average cluster size from 10 UpdGal4, UASEcadRNAi movies ( Fig.…”

Primordial germ cell migration and the Wnt signaling pathway

“…Despite the use of different molecular and genetic pathways depending on cell type and species, the underlying principles of collective cell migration are conserved. The defining feature of this form of cell movement is the maintenance of stable cell-cell contacts between neighboring motile cells (Hegerfeldt et al, 2002;Ulrich et al, 2005;Llense and Martín-Blanco, 2008). Through these interactions, cells of the collective are able to DOI: 10.21451/1984-3143-AR904 specialize leaders and followers, propagate directional cues, and maintain polarity within the group (Scarpa and Mayor, 2016).…”