Defining BMP functions in the hair follicle by conditional ablation of BMP receptor IA

The study demonstrated that BMP receptor IA was crucial for the differentiation of progenitor cells in the inner root sheath and hair shaft in mice. The absence of BMPRIA led to down-regulation of GATA-3 and disrupted IRS differentiation, while Lef1 was up-regulated but unable to control hair differentiation due to a failure to activate Lef1/β-catenin–regulated genes. However, Wnt-mediated transcriptional activation could be restored in BMPRIA-null keratinocytes by introducing a constitutively activated β-catenin, indicating the blockage occurred downstream of Lef1 expression but upstream of β-catenin stabilization. The findings suggested that a sequential inhibition and activation of BMPRIA was necessary to define hair progenitor cells capable of activating hair-specific keratin genes and forming the hair shaft.