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The notochord is a midline structure common to all chordate animals; it provides mechanical and signaling cues for the developing embryo. In vertebrates, the notochord plays key functions during embryogenesis, being a source of developmental signals that pattern the surrounding tissues. It is composed of a core of vacuolated cells surrounded by an epithelial-like sheath of cells that secrete a thick peri-notochordal basement membrane made of different extracellular matrix (ECM) proteins. The correct deposition and organization of the ECM is essential for proper notochord morphogenesis and function. Work carried out in the past two decades has allowed researchers to dissect the contribution of different ECM components to this embryonic tissue. Here, we will provide an overview of these genetic and mechanistic studies. In particular, we highlight the specific functions of distinct matrix molecules in regulating notochord development and notochordderived signals. Moreover, we also discuss the involvement of ECM synthesis and its remodeling in the pathogenesis of chordoma, a malignant bone cancer that originates from remnants of notochord remaining after embryogenesis. KEY WORDS: Basement membrane, Chordoma, Extracellular matrix, Notochord The extracellular matrix (ECM) represents a key component of the microenvironment and is composed of secreted proteins and polysaccharides that are assembled locally into an organized network to which cells adhere (Hynes, 2012). The ECM is well known for its ability to provide structural support for organs and tissues, as well as being a substrate for adhesion and migration for individual cells, and it also forms specialized structures such as basement membranes (BMs). The role of the ECM in cell adhesion and signaling through different receptors, including integrins, has received much attention (Berrier and Yamada, 2007; Legate et al., 2009). The biomechanical properties of the ECM, such as its stiffness and deformability, have also been recognized to provide key inputs for cell behavior (Discher et al., 2009; Gattazzo et al., 2014; Dupont, 2016). Thus, ECM macromolecules and the scaffolds they form have major roles in the proliferation, differentiation, survival, polarity and migration of cells. ECMderived signals are arguably at least as important as soluble signals in governing different cell processes (Hynes, 2009). As a matter of fact, the ECM is also able to position, concentrate, sequester and store growth factors and other signaling molecules. Possible consequences of these interactions are to restrict or promote access of ligands to related cell surface receptors, as well as to allow