Local delivery of TGF beta2 can substitute for placode epithelium to induce mesenchymal condensation during skin appendage morphogenesis.

Development of skin appendages requires interactions between the epithelium and mesenchyme. Without the epithelium, dermal condensations cannot develop, and those already formed will disintegrate. Here we explored the molecular basis of this epithelial requirement and tried to identify the molecule(s) responsible by using the chick feather bud development as a model. TGF beta2 is a likely candidate because its message is predominantly expressed in the feather bud epithelium, and the protein is enriched in the dermal-epidermal junction within the bud. We tested this hypothesis by placing TGF beta-soaked beads on skin explants. We found that TGF beta2, but not TGF beta1, beads placed on top of epithelially stripped mesenchymes can induce dermal condensations. NCAM and tenascin-C (Tn-C) are expressed and protein kinase C is suppressed in the normal feather bud domain. This molecular organization is lost in denuded mesenchyme but can be restored by TGF beta2-coated beads. Subsequently, the TGF beta2-induced dermal condensations can induce nascent epithelium to form skin appendages. Together with our recent findings that ectopic Sonic hedgehog (Shh) expression causes wider TGF beta expression and larger dermal condensation, these results strongly suggest that TGF beta2 produced by epithelial placode is downstream to Shh and plays a key role in the induction of dermal condensation by activating the expression of NCAM and Tn-C, and by suppressing PKC expression.