The multiple, complex roles of versican and its proteolytic turnover by ADAMTS proteases during embryogenesis

• Published in: Matrix biology Vol. 35; pp. 34 - 41
• Main Authors: Nandadasa, Sumeda, Foulcer, Simon, Apte, Suneel S.
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier B.V 01.04.2014
• Subjects: A disintegrin-like and metalloprotease domain with thrombospondin type 1 motifs; ADAM Proteins - metabolism; ADAMTS; Animals; Biological Evolution; Cardiac jelly; Cell Movement - physiology; Cleft palate; Embryogenesis; Embryonic Development - physiology; Extracellular Matrix - chemistry; Extracellular Matrix - physiology; Extremities - embryology; Heart - embryology; Heart valve; Limb development; Melanoblast; Mice; Mice, Transgenic; Models, Biological; Neural Crest - embryology; Palate - embryology; Proteolysis; Soft tissue syndactyly; Versican; Versicans - genetics; Versicans - metabolism; Versicans - physiology; Cleft palate; Soft tissue syndactyly; ADAMTS; Melanoblast; GAG; Heart valve; ECM; CS; A disintegrin-like and metalloprotease domain with thrombospondin type 1 motifs; Embryogenesis; Cardiac jelly; HA; Versican; Limb development
• ISSN: 0945-053X; 1569-1802
• DOI: 10.1016/j.matbio.2014.01.005

Embryonic development is an exceptionally dynamic process, requiring a provisional extracellular matrix that is amenable to rapid remodeling, and proteolytic or non-proteolytic mechanisms that can remodel the major components of this matrix. Versican is a chondroitin-sulfate proteoglycan that forms highly hydrated complexes with hyaluronan and is widely distributed in the provisional matrix of mammalian embryos. It has been extensively studied in the context of cardiovascular morphogenesis, neural crest cell migration and skeletal development. Analysis of Vcan transgenic mice has established the requirement for versican in cardiac development and its role in skeletogenesis. The ADAMTS family includes several versican-degrading proteases that are active during remodeling of the embryonic provisional matrix, especially during sculpting of versican-rich tissues. Versican is cleaved at specific peptide bonds by ADAMTS proteases, and the cleavage products are detectable by neo-epitope antibodies. Myocardial compaction, closure of the secondary palate (in which neural crest derived cells participate), endocardial cushion remodeling, myogenesis and interdigital web regression are developmental contexts in which ADAMTS-mediated versican proteolysis has been identified as a crucial requirement. ADAMTS proteases are expressed coordinately and function cooperatively in many of these contexts. In addition to versican clearance, ADAMTS proteases generate a bioactive versican fragment containing the N-terminal G1 domain, which we have named versikine. This review promotes the view that the embryonic extracellular matrix has evolved not only to provide a permissive environment for embryo growth and morphogenesis, but through its dissolution to influence and regulate cellular processes. •Versican is a widespread component of the embryonic provisional matrix.•ADAMTS proteases cleave versican at specific sites.•Versican proteolysis by ADAMTS proteases is crucial for embryonic remodeling.•Two or more ADAMTS proteases may cleave versican cooperatively in some contexts.•Products of versican proteolysis may be bioactive in embryogenesis.