Hyaluronan and Hyaladherins in Limb Development.
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概要
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Extracellular matrices in which cells migrate and proliferate during embryonic development are enriched in hyaluronan. Hyaluronan-binding proteins, termed hyaladherins, are a group of related proteins that serve as structural components of these extracellular matrices and as receptors at the surface of the cells therein. Recent evidence indicates that these proteins are involved in assembly of hyaluronan-rich, pericellular matrices and in aspects of cell behavior, especially cell migration and aggregation. Mesodermal cells of the early developing limb are surrounded by a hyaluronan-rich matrix, the production of which is regulated by basic fibroblast growth factor (FGF). When the cells of the chondrogenic and myogenic regions of the mesoderm condense, the cells produce less hyaluronan and become separated by a smaller volume of matrix. FGF levels diminish in the limb at this time but an FGF-like factor produced by the ectoderm maintains the high level of hyaluronan present in the periphery of the limb. Also at the condensation stage, the mesodermal cells exhibit increased levels of hyaluronanbinding sites on their surface. Endogenous cell surface hyaluronan bound to these sites can crossbridge adjacent cells, adhering them to one another, due to multivalent binding. Thus condensation can be explained, at least in part, by three facets of hyaluronan-cell interactions: 1) receptor-mediated endocytosis of pre-existing pericellular hyaluronan; 2) decreased hyaluronan production leading to cessation of coat production; 3) stabilization of the condensate by hyaluronan-receptor crossbridging. During differentiation of the condensed mesoderm to cartilage, hyaluronan-binding sites persist on the cell surface. These sites are also essential for assembly of the pericellular matrix surrounding chondrocytes.
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