SUMMARY The activity of keratinocytes in the hair follicle is regulated by signals from a specialized mesenchymal niche, the dermal papilla. Here, mice expressing cre recombinase in the dermal papilla were developed to probe the interaction between follicular keratinocyte populations and the dermal papilla in vivo. Inactivation of the β-catenin gene within the dermal papilla of fully developed hair follicles results in dramatically reduced proliferation of the progenitors and their immediate progeny that generate the hair shaft and, subsequently, premature induction of the destructive phase of the hair cycle (catagen). It also prevents regeneration of the cycling follicle from stem cells resident in the permanent portion of the follicle. Gene expression analysis reveals that β-catenin activity in the dermal papilla regulates at least two signaling pathways, FGF and IGF, that can mediate the inductive effects of the DP on keratinocytes. This study reveals a reciprocal signaling loop that employs Wnt/β-catenin signaling in both epithelial progenitor cells and their mesenchymal niche to govern and coordinate the interactions that are essential for the function of these two compartments.

The hair follicle is a model system for studying epithelial-mesenchymal interactions during organogenesis. Although analysis of the epithelial contribution to these interactions has progressed rapidly, the lack of tools to manipulate gene expression in the mesenchymal component, the dermal papilla, has hampered progress towards understanding the contribution of these cells. In this work, Corin was identified in a screen to detect genes specifically expressed in the dermal papilla. It is expressed in the dermal papilla of all pelage hair follicle types from the earliest stages of their formation, but is not expressed elsewhere in the skin. Mutation of the Corin gene reveals that it is not required for morphogenesis of the hair follicle. However, analysis of the 'dirty blonde' phenotype of these mice reveals that the transmembrane protease encoded by Corin plays a critical role in specifying coat color and acts downstream of agouti gene expression as a suppressor of the agouti pathway.

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