Abstract
Cells in multicellular organisms are surrounded by a complex three-dimensional macromolecular extracellular matrix (ECM). This matrix, traditionally thought to serve a structural function providing support and strength to cells within tissues, is increasingly being recognized as having pleiotropic effects in development and growth. Elucidation of the role that the ECM plays in developmental processes has been significantly advanced by studying the phenotypic and developmental consequences of specific genetic alterations of ECM components in the mouse. These studies have revealed the enormous contribution of the ECM to the regulation of key processes in morphogenesis and organogenesis, such as cell adhesion, proliferation, specification, migration, survival, and differentiation. The ECM interacts with signaling molecules and morphogens thereby modulating their activities. This review considers these advances in our understanding of the function of ECM proteins during development, extending beyond their structural capacity, to embrace their new roles in intercellula signaling.
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The authors are supported by the University Grants Committee of Hong Kong Area of Excellence programme AoE/M-04/04.
Box 1: introduction to some basic ECM molecules and structures
Box 1: introduction to some basic ECM molecules and structures
Collagens
Collagens are triple helical proteins that confer compressive and tensile strength to animal tissues and serve as anchors for cell adhesion through surface receptors. To date, more than 40 mammalian genes encoding collagen α chains have been described, the products of which combine to form at least 28 distinct homo- and heterotrimeric molecules (Myllyharju and Kivirikko 2004; Heino 2007; Gordon and Hahn 2009). The collagen proteins differ considerably in size, structure, tissue distribution, and function, but all are characterized by the presence of either continuous or interrupted triple-helical domains made up of repeating Gly–X–Y motifs. Collagen subfamily members form different supramolecular structures such as fibrils (collagens I, II, III, V, XI, XXIV, and XXVII), non-fibrillar networks (collagen IV), and lattices (collagens VIII and X). Other subfamilies include fibril-associated collagens (collagens VII, IX, XII, XIV, XVI, XIX, XX, XXI, and XXII) and transmembranous collagens (collagen XIII, XVII, XXIII, and XXV).
Proteoglycans
Proteoglycans (PGs) consist of a diverse group of core proteins to which sulfated glycosaminoglycan (GAG) side chains are covalently linked. The GAG chains can be classified as keratin sulfate, chondroitin sulfate (CS), dermatan sulfate, and heparan sulfate (HS; Bulow and Hobert 2006). PGs can be secreted or cell-surface bound and serve diverse functions including ECM assembly and mediating cell adhesion and motility. PGs can be generally classified according to the major GAG chains they carry. For example, perlecan is classified as HSPG but may also carry a CS chain, especially when expressed in cartilage in which the CS may modulate FGF signaling (Smith et al. 2007a).
Basement membrane, laminin, and collagen IV
Basement membrane (BM) is a specialized ECM comprising laminins and collagen IV networks as central structural components, and nidogens and PGs. It is present in many tissues and serves as a barrier and structural support. Diversity of BM structure is partly derived from the large numbers of differentially expressed isoforms of laminins. Laminin isoforms are a family of 15 multidomain heterotrimeric glycoproteins, each assembled from a combination of five α, three β, and three γ chains (Nguyen and Senior 2006). The nomenclature for the laminins is based on chain numbers, e.g., laminin composed of α3β3γ2, formerly known as laminin-5, is now called laminin-332 (Aumailley et al. 2005). Collagen IV is a heterotrimeric protomer of three isoforms with the “classic” isoform α12α2(IV) present in BM of most tissues (Yurchenco et al. 2004; Khoshnoodi et al. 2008).
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Tsang, K.Y., Cheung, M.C.H., Chan, D. et al. The developmental roles of the extracellular matrix: beyond structure to regulation. Cell Tissue Res 339, 93–110 (2010). https://doi.org/10.1007/s00441-009-0893-8
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DOI: https://doi.org/10.1007/s00441-009-0893-8