Interactions between growth factors and gap junctional communication in developing systems

In the vertebrate limb bud fibroblast growth factor (FGF) 4 secreted by cells of the posterior apical ectodermal ridge controls digit pattern, which is directed by polarizing cells in the posterior mesenchyme at the tip of the bud. FGF4 also controls the expression of gap junctions in the limb. Both chick and mouse limb bud mesenchyme express connexin 32 (Cx32; beta(1)) and Cx43 (alpha(1)), although not in the same gap junction plaques. Quantitative analysis reveals two gradients of gap junctions: from posterior to anterior in the subapical mesenchyme and from distal to proximal along the bud. The highest gap junction density is associated with the polarizing region. Micromass cultures of chick and mouse posterior and anterior mesenchyme cells were used to assess the ability of FGF4 to modulate gap junctional communication. Posterior mesenchyme (polarizing region) cells express a population of gap junctions that are highly sensitive to FGF4, whereas gap junctions between anterior mesenchyme cells are completely insensitive to FGF4. FGF4 doubles gap junction density, intercellular communication and the polarizing capacity of posterior mesenchyme cells, restoring polarizing capacity to in vitro levels. We conclude that gap junctional communication and polarizing capacity are intimately linked. Interactions between signalling molecules and junctional communication may play an important role in controlling development.