The Vitamin D Receptor Is Required for Activation of CWnt and Hedgehog Signaling in Keratinocytes

The study found that the absence of the vitamin D receptor (VDR) in mice led to alopecia due to the lack of ligand-independent actions necessary for initiating postmorphogenic hair cycles. The research showed that VDR-null mice had significantly reduced induction of cWnt and hedgehog target genes during early anagen compared to wild-type mice. In vitro studies with primary keratinocytes revealed impaired cWnt target gene induction in VDR(-/-) keratinocytes. Chromatin immunoprecipitation analyses indicated that the VDR was recruited to the regulatory regions of cWnt and hedgehog target genes in wild-type keratinocytes, but not in VDR(-/-) or Lef1(-/-) keratinocytes. In vivo, hedgehog pathway activation could not compensate for the cWnt signaling defect in VDR(-/-) mice. The findings demonstrated that the unliganded VDR is crucial for the activation of cWnt and hedgehog signaling pathways during the postnatal hair cycle.