ECTODERMAL STIMULATION OF THE PRODUCTION OF HYALURONAN-DEPENDENT PERICELLULAR MATRIX BY EMBRYONIC LIMB MESODERMAL CELLS

Interaction of ectoderm and underlying mesoderm is essential for norma l vertebrate limb morphogenesis. One of the functions of Limb bud ecto derm is its influence on the composition of extracellular matrix in su bectodermal mesoderm, which in turn participates in morphogenesis of t his region of the limb. This matrix is highly enriched in hyaluronan, even at the time when the level of hyaluronan in the chondrogenic and myogenic regions of the limb decreases, due to secretion of a stimulat ory factor by the ectoderm, In this study we show that limb bud ectode rm not only stimulates hyaluronan synthesis but induces formation of l arge hyaluronan-dependent, pericellular matrices around cultured limb bud mesodermal cells. The ectodermal activity is mimicked in great par t by fibroblast growth factor-2 and transforming growth factor-beta, a nd antibodies to these proteins inhibit induction of mesodermal perice llular matrix by the ectodermal factor, It has been shown by other inv estigators that fibroblast growth factor-a is produced by Limb ectoder m whereas transforming growth factor-p is present in limb mesodermal t issues. Thus we conclude that the unique properties of mesodermally pr oduced matrix underlying limb bud ectoderm are regulated, at least in part, by ectodermal fibroblast growth factor-a, probably in concert wi th mesodermal transforming growth factor-beta. (C) 1995 Wiley-Liss, In c.