Basement Membranes in the Worm

Abstract

The nematode worm Caenorhabditis elegans has all the major basement membrane proteins found in vertebrates, usually with a smaller gene family encoding each component. With its powerful forward genetics, optical clarity, simple tissue organization, and the capability to functionally tag most basement membrane components with fluorescent proteins, C. elegans has facilitated novel insights into the assembly and function of basement membranes. Although basement membranes are generally thought of as static structures, studies in C. elegans have revealed their active properties and essential functions in tissue formation and maintenance. Here we review discoveries from C. elegans development that highlight dynamic aspects of basement membrane assembly, function, and regulation during organ growth, tissue polarity, cell migration, cell invasion, and tissue attachment. These studies have helped transform our view of basement membranes from static support structures to dynamic scaffoldings that play broad roles in regulating tissue organization and cellular behavior that are essential for development and have important implications in human diseases.

Characterization ofDrosophila Nidogen/entactinreveals roles in basement membrane stability, barrier function and nervous system patterning

“…Nidogen mutants generated in C. elegans and mouse are viable and display only mild phenotypes (Bader et al, 2005;Böse et al, 2006;Dong et al, 2002;Kang and Kramer, 2000;Murshed et al, 2000;Schymeinsky et al, 2002), a surprising finding that is in strong contrast to the essential developmental roles demonstrated for the other BM molecules (Arikawa-Hirasawa et al, 1999;Clay and Sherwood, 2015;Poschl et al, 2004;Yao, 2017). In agreement with these former observations, Drosophila Ndg Δ mutants were viable and fertile, and could be maintained as homozygous stocks.…”

α-Integrins dictate distinct modes of type IV collagen recruitment to basement membranes

“…The diversity in BMs regulates key cell and tissue properties, including cell polarity, cell differentiation, cell survival, tissue shaping, filtration, and resistance to mechanical stresses ( Breitkreutz et al, 2013 ). How diverse BMs are constructed on tissues is not well understood, particularly as many BM components are expressed and secreted from distant sources and selectively acquired from the extracellular fluid ( Glentis et al, 2014 ; Clay and Sherwood, 2015 ).…”

“…Laminin and type IV collagen are essential for embryonic animal development, hindering postembryonic studies. Further, in vertebrates there are three distinct type IV collagens, 16 laminins, and at least 24 integrin αβ heterodimer receptors, making interpretation of genetic analysis daunting ( Clay and Sherwood, 2015 ). In addition, BM components and receptors have not yet been tagged in vertebrates with genetically encoded fluorescent proteins to dynamically examine their localization ( Kelley et al, 2014 ).…”

Genetic Suppression of Basement Membrane Defects inCaenorhabditis elegansby Gain of Function in Extracellular Matrix and Cell-Matrix Attachment Genes

“…Assembly of the first BMs in the early embryo involves a series of partly independent yet coordinated self-assembly processes. Laminin, type IV collagen, heparan sulfate proteoglycans (HSPGs) and nidogen are the most prominent and conserved protein components of BMs ( Yurchenco 2011 ; Clay and Sherwood 2015 ; Fidler et al 2017 ). Laminins are required for initial BM assembly, and self-assemble into a cell-associated network independently of type IV collagen, as reviewed in Hohenester and Yurchenco (2013) .…”