Boundary cells restrict dystroglycan trafficking to control basement membrane sliding during tissue remodeling.

Shelly TH McClatchey,David R Sherwood,Alan Chen,Qiuyi Chi,Zheng Wang,Eric L Hastie,Wanqing Shen,Lara M Linden,Lin Wang

doi:10.7554/elife.17218

Shelly TH McClatchey, David R Sherwood + Show 7 more

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https://doi.org/10.7554/elife.17218

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Abstract

Epithelial cells and their underlying basement membranes (BMs) slide along each other to renew epithelia, shape organs, and enlarge BM openings. How BM sliding is controlled, however, is poorly understood. Using genetic and live cell imaging approaches during uterine-vulval attachment in C. elegans, we have discovered that the invasive uterine anchor cell activates Notch signaling in neighboring uterine cells at the boundary of the BM gap through which it invades to promote BM sliding. Through an RNAi screen, we found that Notch activation upregulates expression of ctg-1, which encodes a Sec14-GOLD protein, a member of the Sec14 phosphatidylinositol-transfer protein superfamily that is implicated in vesicle trafficking. Through photobleaching, targeted knockdown, and cell-specific rescue, our results suggest that CTG-1 restricts BM adhesion receptor DGN-1 (dystroglycan) trafficking to the cell-BM interface, which promotes BM sliding. Together, these studies reveal a new morphogenetic signaling pathway that controls BM sliding to remodel tissues.

Highlights

The basement membrane (BM) is a cell-associated, dense, sheet-like form of extracellular matrix that underlies all epithelia and endothelial tissue, and surrounds muscle, fat, and Schwann cells (Halfter et al, 2015; Yurchenco, 2011)
The rapid expansion and invagination of the vulval cells generate forces on the BM that promote expansion of the nascent BM opening through BM sliding over the vulval and uterine cells that sit at the boundary of the BM gap
We determined if the increase of DGN-1 at the cell-BM interface in the lin-29 mutant could be responsible for stronger adhesion of the uterine cells to the BM, causing BM sliding to fail. Consistent with this idea, reduction of dgn-1 expression via uterine specific RNAi in the lin-29(qy1) mutant restored BM sliding and gap expansion (Figure 8D,E). These results suggest that LIN-29 activity in the anchor cell (AC) leads to LAG-2/LIN-12 (Notch)-mediated upregulation of ctg-1 expression in the uterine p cells that restricts the cell surface trafficking and accumulation of the BM receptor DGN-1, which facilitates BM sliding during uterine-vulval attachment

Summary

Introduction

The basement membrane (BM) is a cell-associated, dense, sheet-like form of extracellular matrix that underlies all epithelia and endothelial tissue, and surrounds muscle, fat, and Schwann cells (Halfter et al, 2015; Yurchenco, 2011). BMs are built on polymeric laminin and type IV collagen networks that arose at the time of animal multicellularity, and may have been required for the evolution of complex tissues (Hynes, 2012; Ozbek et al, 2010). Consistent with this idea, BMs provide tissues with mechanical support, barrier functions, and cues for polarization, differentiation and growth (Breitkreutz et al, 2013; Hay, 1981; Poschl et al, 2004; Rasmussen et al, 2012; Suh and Miner, 2013; Yurchenco, 2011). Examples of cell-BM sliding are varied and include egg chamber rotation in Drosophila, where the follicle cells move along BM and deposit constricting strips of aligned type IV collagen, which direct egg elongation along the anterior-posterior axis

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