A moving source of matrix components is essential for De Novo basement membrane formation Journal Article


Author(s): Matsubayashi, Yutaka; Louani, Adam; Dragu, Anca; Sanchez-Sanchez, Besaiz J; Serna Morales, Eduardo; Yolland, Lawrence; György, Attila; Vizcay, Gema; Fleck, Roland A; Heddleston, John M; Chew, Teng-Leong; Siekhaus, Daria E; Stramer, Brian M
Article Title: A moving source of matrix components is essential for De Novo basement membrane formation
Affiliation IST Austria
Abstract: The basement membrane (BM) is a thin layer of extracellular matrix (ECM) beneath nearly all epithelial cell types that is critical for cellular and tissue function. It is composed of numerous components conserved among all bilaterians [1]; however, it is unknown how all of these components are generated and subsequently constructed to form a fully mature BM in the living animal. Although BM formation is thought to simply involve a process of self-assembly [2], this concept suffers from a number of logistical issues when considering its construction in vivo. First, incorporation of BM components appears to be hierarchical [3-5], yet it is unclear whether their production during embryogenesis must also be regulated in a temporal fashion. Second, many BM proteins are produced not only by the cells residing on the BM but also by surrounding cell types [6-9], and it is unclear how large, possibly insoluble protein complexes [10] are delivered into the matrix. Here we exploit our ability to live image and genetically dissect de novo BM formation during Drosophila development. This reveals that there is a temporal hierarchy of BM protein production that is essential for proper component incorporation. Furthermore, we show that BM components require secretion by migrating macrophages (hemocytes) during their developmental dispersal, which is critical for embryogenesis. Indeed, hemocyte migration is essential to deliver a subset of ECM components evenly throughout the embryo. This reveals that de novo BM construction requires a combination of both production and distribution logistics allowing for the timely delivery of core components.
Keywords: Basement Membrane; Drosophila; extracellular matrix; cell migration; morphogenesis; Macrophage; hemocyte; collagen IV; laminin; perlecan
Journal Title: Current Biology
Volume: 27
Issue 22
ISSN: 0960-9822
Publisher: Cell Press  
Date Published: 2017-11-09
Start Page: 3526
End Page: 3534
Copyright Statement: CC BY 4.0
URL:
DOI: 10.1016/j.cub.2017.10.001
Notes: We thank Paul Martin, Helen Weavers, Anna Franz, and David Umulis for comments on the manuscript. We also thank Franck Schnorrer, Maria Martin-Bermudo, Will Wood, Marc Dionne, Jürgen Heinisch, Leonie Ringrose, Katja Brückner, and Clemens Cabernard for Drosophila reagents; Guy Tear for assistance with embryo fillet preparations; and Todd Laverty for Drosophila stock support at the Janelia Research Campus. B.M.S. is supported by the Biotechnology and Biological Sciences Research Council (BBSRC) (grant BB/L021927/1) and the Wellcome Trust (grant 107859/Z/15/Z). The lattice light-sheet microscope imaging experiments were performed at the Advanced Imaging Center (AIC) at Howard Hughes Medical Institute Janelia Research Campus. The AIC is jointly supported by the Gordon and Betty Moore Foundation and HHMI.
Open access: yes (OA journal)