title: Extracellular distribution of diffusible growth factors controlled by heparan sulfate proteoglycans during mammalian embryogenesis.
abstract: During mouse embryogenesis, diffusible growth factors, i.e. fibroblast growth factors, Wnt, bone morphogenetic protein and Hedgehog family members, emanating from localized areas can travel through the extracellular space and reach their target cells to specify the cell fate and form tissue architectures in coordination. However, the mechanisms by which these growth factors travel great distances to their target cells and control the signalling activity as morphogens remain an enigma. Recent studies in mice and other model animals have revealed that heparan sulfate proteoglycans (HSPGs) located on the cell surface (e.g. syndecans and glypicans) and in the extracellular matrix (ECM; e.g. perlecan and agrin) play crucial roles in the extracellular distribution of growth factors. Principally, the function of HSPGs depends primarily on the fine features and localization of their heparan sulfate glycosaminoglycan chains. Cell-surface-tethered HSPGs retain growth factors as co-receptors and/or endocytosis mediators, and enzymatic release of HSPGs from the cell membrane allows HSPGs to transport or move multiple growth factors. By contrast, ECM-associated HSPGs function as a reservoir or barrier in a context-dependent manner. This review is focused on our current understanding of the extracellular distribution of multiple growth factors controlled by HSPGs in mammalian development.
authors.affiliation: Department of Molecular Embryology, Osaka Medical Center and Research Institute for Maternal and Child Health, Osaka Prefectural Hospital Organization, 840 Murodo-cho, Izumi, Osaka 594-1101, Japan imatsuo@mch.pref.osaka.jp.
authors.forename: Isao
authors.initials: I
authors.lastname: Matsuo
authors.affiliation: Department of Molecular Embryology, Osaka Medical Center and Research Institute for Maternal and Child Health, Osaka Prefectural Hospital Organization, 840 Murodo-cho, Izumi, Osaka 594-1101, Japan.
authors.forename: Chiharu
authors.initials: C
authors.lastname: Kimura-Yoshida
mesh_terms: D000818:Animals; D001692:Biological Transport / Q000502:physiology; D047108:Embryonic Development / Q000502:physiology*; D005110:Extracellular Space / Q000378:metabolism*; D019812:Heparan Sulfate Proteoglycans / Q000096:biosynthesis / Q000737:chemistry / Q000378:metabolism*; D036341:Intercellular Signaling Peptides and Proteins / Q000378:metabolism*; D051379:Mice; D008954:Models, Biological; D015398:Signal Transduction / Q000502:physiology*
chemical_list: D019812:Heparan Sulfate Proteoglycans; D036341:Intercellular Signaling Peptides and Proteins
keywords: diffusible growth factors; embryogenesis; extracellular matrix; heparan sulfate proteoglycans; mouse; shedding