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© The Rockefeller University Press,
0021-9525/1997//1125 $5.00
The Journal of Cell Biology, Volume 138, Number 5,
, 1997 1125-1137
Article |
Fibroblast Growth Factor 4 Directs Gap Junction Expression in the Mesenchyme of the Vertebrate Limb Bud
Pattern in the developing limb depends on signaling by polarizing region mesenchyme cells, which are located at the posterior margin of the bud tip. Here we address the underlying cellular mechanisms. We show in the intact bud that connexin 43 (Cx43) and Cx32 gap junctions are at higher density between distal posterior mesenchyme cells at the tip of the bud than between either distal anterior or proximal mesenchyme cells. These gradients disappear when the apical ectodermal ridge (AER) is removed. Fibroblast growth factor 4 (FGF4) produced by posterior AER cells controls signaling by polarizing cells. We find that FGF4 doubles gap junction density and substantially improves functional coupling between cultured posterior mesenchyme cells. FGF4 has no effect on cultured anterior mesenchyme, suggesting that any effects of FGF4 on responding anterior mesenchyme cells are not mediated by a change in gap junction density or functional communication through gap junctions. In condensing mesenchyme cells, connexin expression is not affected by FGF4. We show that posterior mesenchyme cells maintained in FGF4 under conditions that increase functional coupling maintain polarizing activity at in vivo levels. Without FGF4, polarizing activity is reduced and the signaling mechanism changes. We conclude that FGF4 regulation of cell–cell communication and polarizing signaling are intimately connected.
Abbreviations used in this paper: AER, apical ectodermal ridge; Cx, connexin; FGF, fibroblast growth factor; HH, Hamilton Hamburger.
Address all correspondence to Anne Warner, Department of Anatomy and Developmental Biology, University College London, Gower Street, London WC1E 6BT UK. Tel.: 171-380-7279. Fax: 171-419-3014. E-mail: a.warner{at}ucl.ac.uk
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