LOCAL-DELIVERY OF TGF BETA-2 CAN SUBSTITUTE FOR PLACODE EPITHELIUM TOINDUCE MESENCHYMAL CONDENSATION DURING SKIN APPENDAGE MORPHOGENESIS

Development of skin appendages requires interactions between the epith elium and mesenchyme. Without the epithelium, dermal condensations can not develop, and those already formed will disintegrate. Here we explo red the molecular basis of this epithelial requirement and tried to id entify the molecule(s) responsible by using the chick feather bud deve lopment as a model. TGF beta 2 is a likely candidate because its messa ge is predominantly expressed in the feather bud epithelium, and the p rotein is enriched in the dermal-epidermal junction within the bud. We tested this hypothesis by placing TGF beta-soaked beads on skin expla nts. We found that TGF beta 2, but not TGF beta 1, 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 supp ressed in the normal feather bud domain. This molecular organization i s lost in denuded mesenchyme but can be restored by TGF beta 2-coated beads. Subsequently, the TGF beta 2-induced dermal condensations can i nduce nascent epithelium to form skin appendages. Together with our re cent findings that ectopic Sonic hedgehog (Shh) expression causes wide r TGF beta expression and larger dermal condensation, these results st rongly suggest that TGF beta 2 produced by epithelial placode is downs tream to Shh and plays a key role in the induction of dermal condensat ion by activating the expression of NCAM and Tn-C, and by suppressing PKC expression. (C) 1996, Academic Press, Inc.