Dynamics of the basement membrane in invasive epithelial clusters inDrosophila

Abstract

The basement membrane (BM) represents a barrier to cell migration, which has to be degraded to promote invasion. However, the role and behaviour of the BM during the development of pre-invasive cells is only poorly understood. Drosophila border cells (BCs) provide an attractive genetic model in which to study the cellular mechanisms underlying the migration of mixed cohorts of epithelial cells. BCs are made of two different epithelial cell types appearing sequentially during oogenesis: the polar cells and the outer BCs. Here, we show that the pre-invasive polar cells undergo an unusual and asymmetrical apical capping with major basement membrane proteins, including the two Drosophila Collagen IV α chains, Laminin A and Perlecan. Capping of polar cells proceeds through a novel, basal-to-apical transcytosis mechanism that involves the small GTPase Drab5. Apical capping is transient and is followed by rapid shedding prior to the initiation of BC migration, suggesting that the apical cap blocks migration. Consistently,non-migratory polar cells remain capped. We further show that JAK/STAT signalling and recruitment of outer BCs are required for correct shedding and migration. The dynamics of the BM represents a marker of migratory BC,revealing a novel developmentally regulated behaviour of BM coupled to epithelial cell invasiveness.

Basement membrane remodeling is essential for Drosophila disc eversion and tumor invasion

“…Consistent with this notion, defects in BM are associated with several diseases, including thickened renal glomerular capillary and tubular BM in diabetes mellitus patients, ectopic expression of embryonic collagen in Alport's kidney syndrome, and loss or overproduction of BM components in muscular dystrophy and rheumatoid arthritis (2,3). The observation that BM exhibits dynamic changes in developing tissues (4,5) and in tumors (6) further suggests that modulation of BM could play a vital role in normal and pathologic processes and might be regulated by signaling events.…”

The endocytic control of JAK/STAT signalling in Drosophila

“…Rab5 has been shown to be involved in basement membrane dynamics and migration of BCs (Medioni and Noselli, 2005), and in epithelial polarity (Lu and Bilder, 2005). Follicle cells mutant for Rab5 showed a strong reduction of cytoplasmic and nuclear STAT accompanied by perinuclear localization (Fig.…”

Asymmetric localisation of cytokine mRNA is essential for JAK/STAT activation during cell invasiveness

“…Indeed, in tissue culture, Upd is mainly found associated with the extracellular matrix (Harrison et al, 1998), which might help to limit Upd diffusion in vivo. Interestingly, it has been reported that a transient cap of extracellular matrix forms at the apical side of PCs when BCs are being recruited (Medioni and Noselli, 2005), raising the possibility of an association of Upd with the extracellular matrix cap for the purposes of building up the gradient.…”