title: Identification of collagen fibril fusion during vertebrate tendon morphogenesis. The process relies on unipolar fibrils and is regulated by collagen-proteoglycan interaction.
abstract: The synthesis of an extracellular matrix containing long (approximately mm in length) collagen fibrils is fundamental to the normal morphogenesis of animal tissues. In this study we have direct evidence that fibroblasts synthesise transient early fibril intermediates (approximately 1 micrometer in length) that interact by tip-to-tip fusion to generate long fibrils seen in older tissues. Examination of early collagen fibrils from tendon showed that two types of early fibrils occur: unipolar fibrils (with carboxyl (C) and amino (N) ends) and bipolar fibrils (with two N-ends). End-to-end fusion requires the C-end of a unipolar fibril. Proteoglycans coated the shafts of the fibrils but not the tips. In the absence of proteoglycans the fibrils aggregated by side-to-side interactions. Therefore, proteoglycans promote tip-to-tip fusion and inhibit side-to-side fusion. This distribution of proteoglycan along the fibril required co-assembly of collagen and proteoglycan prior to fibril assembly. The study showed that collagen fibrillogenesis is a hierarchical process that depends on the unique structure of unipolar fibrils and a novel function of proteoglycans.
authors.affiliation: Wellcome Trust Centre for Cell-Matrix Research, School of Biological Sciences, University of Manchester, 2.205 Stopford Building, Oxford Road, Manchester, M13 9PT, UK.
authors.forename: H K
authors.initials: HK
authors.lastname: Graham
authors.forename: D F
authors.initials: DF
authors.lastname: Holmes
authors.forename: R B
authors.initials: RB
authors.lastname: Watson
authors.forename: K E
authors.initials: KE
authors.lastname: Kadler
mesh_terms: D000818:Animals; D002642:Chick Embryo; D003094:Collagen / Q000737:chemistry / Q000502:physiology* / Q000648:ultrastructure; D006909:Hydroxyproline / Q000032:analysis; D008854:Microscopy, Electron; D017348:Microscopy, Electron, Scanning Transmission; D009024:Morphogenesis; D011509:Proteoglycans / Q000737:chemistry; D013710:Tendons / Q000196:embryology* / Q000648:ultrastructure; D014714:Vertebrates
chemical_list: D011509:Proteoglycans; D003094:Collagen; D006909:Hydroxyproline