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Matrix Biol,
2000]
Integrins are essential for the development of the two genetically tractable invertebrate model organisms, the nematode worm Caenorhabditis elegans and the fruit fly Drosophila melanogaster. Just two integrins are present in C. elegans: one putative RGD binding integrin alphapat-2betapat-3, corresponding to Drosophila alphaPS2betaPS and vertebrate alpha5beta1, alphaVbeta1 and alpha8beta1, and one putative laminin binding integrin alphaina-1betapat-3, corresponding to Drosophila alphaPS1betaPS and vertebrate alpha3beta1, alpha6beta1 and alpha7beta1. In this review, the function of this minimal set of integrins during the development of these two invertebrates is compared. Despite the differences in bodyplan and developmental strategy, integrin adhesion to the extracellular matrix is required for similar processes: the formation of the link that translates muscle contraction into movement of the exoskeleton, cell migration, and morphogenetic interactions between epithelia. Other integrin functions, such as regulation of gene expression, have not yet been experimentally demonstrated in both organisms. Additional proteins have been characterised in each organism that are essential for integrin function, including extracellular matrix ligands and intracellular interacting proteins, but so far different proteins have been found in the two organisms. This in part represents the fact that the characterisation of the full set of interacting proteins is not complete in either system. However, in other cases different proteins appear to be used for similar functions in the two animals. The continued use of genetic approaches to identify proteins required for integrin function in these two model organisms should lead to the identification of the minimal set of conserved components that form integrin adhesive structures.
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Organogenesis,
2012]
The extracellular matrix (ECM) plays an essential role in organizing tissues, defining their shapes or in presenting growth factors. Their components have been well described in most species, but our understanding of the mechanisms that control ECM remodeling remains limited. Likewise, how the ECM contributes to cellular mechanical responses has been examined in few cases. Here, I review how studies performed in C. elegans have brought several significant advances on those topics. Focusing only on epithelial cells, I discuss basement membrane invasion by the anchor cell during vulva morphogenesis, a process that has greatly expanded our knowledge of ECM remodeling in vivo. I then discuss the ECM role in a novel mechanotransduction process, whereby muscle contractions stimulate the remodeling of hemidesmosome-like junctions in the epidermis, which highlights that these junctions are mechanosensitive. Finally, I discuss progress in defining the composition and potential roles of the apical ECM covering epidermal cells in embryos.
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Annu Rev Genet,
1994]
All metazoans possess extracellular matrices (ECM) composed of complex assemblies of molecules with generally well conserved structures and functions. ECM play structural roles, providing scaffolds that organize and strengthen tissues, and instructional roles, influencing differentiation and development. Major ECM components include the collagens, a diverse family of fibrous proteins distinguished by their triple-helical coiled coil structure, other large glycoproteins, such as laminin, fibronectin and nidogen, and proteoglycans, proteins with attached glycosaminoglycan chains. For most ECM components, cell surface receptors have been identified that can mediate interactions between the cell and its ECM. The nematode Caenorhabditis elegans is an excellent system for studies of the structures and functions of ECM components, and their roles in development. C. elegans is the simplest metazoan in which detailed genetic analysis of the ECM can be performed. The complete cell lineage and detailed anatomical structure of the organism have been described. The simple life style of C. elegans allows animals with severe morphological and/or motility defects to survive and, because they are internally self-fertilizing hermaphrodites, even reproduce. These properties can simplify mutational analyses of genes encoding ECM components. Two major forms of ECM have been identified in C. elegans, the cuticle and basement membranes. The cuticle, or exoskeleton, covers the outside of the animal and lines the lumen of the pharynx. Basement membranes cover the pseudocoelomic faces of the pharynx, intestine, gonad, and hypodermis. There is no visible interstitial matrix between the cells within tissues, possibly because nearly all cells are adjacent to the cuticle or a basement membrane. This review focuses on studies of the ECM in C. elegans. The reader is referred to excellent recent reviews concerning related topics: collagens in other nematodes; mutations in human fibrillar collagens; mutations in human type IV collagen; composition
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Worm,
2017]
Molting is an essential developmental process for the majority of animal species on Earth. During the molting process, which is a specialized form of extracellular matrix (ECM) remodeling, the old apical ECM, or cuticle, is replaced with a new one. Many of the genes and pathways identified as important for molting in nematodes are highly conserved in vertebrates and include regulators and components of vesicular trafficking, steroid-hormone signaling, developmental timers, and hedgehog-like signaling. In this review, we discuss what is known about molting, with a focus on studies in Caenorhabditis elegans. We also describe the key structural elements of the cuticle that must be released, newly synthesized, or remodeled for proper molting to occur.
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WormBook,
2007]
The nematode cuticle is an extremely flexible and resilient exoskeleton that permits locomotion via attachment to muscle, confers environmental protection and allows growth by molting. It is synthesised five times, once in the embryo and subsequently at the end of each larval stage prior to molting. It is a highly structured extra-cellular matrix (ECM), composed predominantly of cross-linked collagens, additional insoluble proteins termed cuticlins, associated glycoproteins and lipids. The cuticle collagens are encoded by a large gene family that are subject to strict patterns of temporal regulation. Cuticle collagen biosynthesis involves numerous co- and post-translational modification, processing, secretion and cross-linking steps that in turn are catalysed by specific enzymes and chaperones. Mutations in individual collagen genes and their biosynthetic pathway components can result in a range of defects from abnormal morphology (dumpy and blister) to embryonic and larval death, confirming an essential role for this structure and highlighting its potential as an ECM experimental model system.
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Dev Dyn,
2010]
Hemidesmosomes are evolutionarily conserved attachment complexes linked to intermediate filaments that connect epithelial cells to the extracellular matrix. They provide tissue integrity and resistance to mechanical forces. Alterations in hemidesmosome structures are responsible for skin blistering, carcinoma invasion, and wound-healing defects. Valuable information about hemidesmosome assembly and disassembly has been obtained from in vitro cell culture studies. However, how these processes take place in vivo still remains elusive. Here, we discuss recent data about the formation and reorganization of hemidesmosomes in several in vivo model systems, particularly zebrafish and Caenorhabditis elegans, focusing on various factors affecting their dynamics. Mechanisms found in different organisms reveal that hemidesmosome formation and maintenance in vivo are carefully controlled by ECM protein folding, ECM-receptor expression and trafficking, and by post-translational modification of hemidesmosome components. These findings validate and extend the in vitro studies, and shed light on our understanding about hemidesmosomes across species.
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J Muscle Res Cell Motil,
2007]
During evolution, both the architecture and the cellular physiology of muscles have been remarkably maintained. Striated muscles of invertebrates, although less complex, strongly resemble vertebrate skeletal muscles. In particular, the basic contractile unit called the sarcomere is almost identical between vertebrates and invertebrates. In vertebrate muscles, sarcomeric actin filaments are anchored to attachment points called Z-disks, which are linked to the extra-cellular matrix (ECM) by a muscle specific focal adhesion site called the costamere. In this review, we focus on the dense body of the animal model Caenorhabditis elegans. The C. elegans dense body is a structure that performs two in one roles at the same time, that of the Z-disk and of the costamere. The dense body is anchored in the muscle membrane and provides rigidity to the muscle by mechanically linking actin filaments to the ECM. In the last few years, it has become increasingly evident that, in addition to its structural role, the dense body also performs a signaling function in muscle cells. In this paper, we review recent advances in the understanding of the C. elegans dense body composition and function.
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Adv Parasitol,
2003]
Nematodes include species that are significant parasites of man, his domestic animals and crops, and cause chronic debilitating diseases in the developing world; such as lymphatic filariasis and river blindness caused by filarial species. Around one third of the World's population harbour parasitic nematodes; no vaccines exist for prevention of infection, limited effective drugs are available and drug resistance is an ever-increasing problem. A critical structure of the nematode is the protective cuticle, a collagen-rich extracellular matrix (ECM) that forms the exoskeleton, and is critical for viability. This resilient structure is synthesized sequentially five times during nematode development and offer protection from the environment, including the hosts' immune response. The detailed characterization of this complex structure; its components, and the means by which they are synthesized, modified, processed and assembled will identify targets that may be exploited in the future control of parasitic nematodes. This review will focus on the nematode cuticle. This structure is predominantly composed of collagens, a class of proteins that are modified by a range of co- and post-translational modifications prior to assembly into higher order complexes or ECMs. The collagens and their associated enzymes have been comprehensively characterized in vertebrate systems and some of these studies will be addressed in this review. Conversely, the biosynthesis of this class of essential structural proteins has not been studied in such detail in the nematodes. As with all morphogenetic, functional and developmental studies in the Nematoda phylum, the free-living species Caenorhabditis elegans has proven to be invaluable in the characterization of the cuticle and the cuticle collagen gene family, and is now proving to be an excellent model in the study of cuticle collagen biosynthetic enzymes. This model system will be the main
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Trends in Cell Biology,
2002]
Interaction of cells with the extracellular matrix (ECM) results in the regulation of cell growth, differentiation and migration by coordinated signal transduction through integrins and growth-factor receptors. Integrins achieve signaling by interaction with intracellular effectors that couple integrins and growth-factor receptors to downstream components. One well-studied effector is focal-adhesion kinase (FAK), but recently another protein kinase, integrin-linked kinase (ILK), has been identified as a receptor-proximal effector of integrin and growth-factor signaling. ILK appears to interact with and be influenced by a number of different signaling pathways, and this provides new routes for integrin-mediatied signaling. This article discusses ILK structure and function and recent genetic and biochemical evidence about the role of ILK in signal transduction.
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J Dev Biol,
2020]
Apical extracellular matrices (aECMs) coat exposed surfaces of epithelia to shape developing tissues and protect them from environmental insults. Despite their widespread importance for human health, aECMs are poorly understood compared to basal and stromal ECMs. The nematode <i>Caenorhabditis elegans</i> contains a variety of distinct aECMs, some of which share many of the same types of components (lipids, lipoproteins, collagens, zona pellucida domain proteins, chondroitin glycosaminoglycans and proteoglycans) with mammalian aECMs. These aECMs include the eggshell, a glycocalyx-like pre-cuticle, both collagenous and chitin-based cuticles, and other understudied aECMs of internal epithelia. <i>C. elegans</i> allows rapid genetic manipulations and live imaging of fluorescently-tagged aECM components, and is therefore providing new insights into aECM structure, trafficking, assembly, and functions in tissue shaping.