Deletion of Hypoxia-Inducible Factor Prolyl 4-Hydroxylase 2 in FoxD1-Lineage Mesenchymal Cells Leads to Congenital Truncal Alopecia

The study demonstrates that the deletion of Hif-p4h-2, a gene encoding for hypoxia-inducible factor prolyl 4-hydroxylase 2 (HIF-P4H-2), in FoxD1-lineage mesenchymal cells disrupts normal hair follicle (HF) development in mice. These cells, which are primarily located in the dermis and form the dermal papilla of HFs, are crucial for HF morphogenesis. The inactivation of Hif-p4h-2 resulted in the formation of epithelial-lined HF cysts and subsequent truncal alopecia due to disturbed HF development during the first catagen phase. This was accompanied by the stabilization of HIF and dysregulation of genes involved in keratin formation, HF differentiation, and key signaling pathways such as HIF, TGF-β, and Notch. The study suggests that the proper functioning of HIF-P4H-2 in FoxD1-lineage cells is essential for maintaining HF development and homeostasis, with its disruption likely affecting the interplay between the HIF, TGF-β, and Notch pathways.