LHX2 Is a Direct NF-κB Target Gene That Promotes Primary Hair Follicle Placode Down-Growth

The study identified LHX2 as a direct target gene of NF-κB that is crucial for primary hair follicle placode down-growth. In mice lacking NF-κB activity, hair follicle pre-placodes formed but failed to proliferate into placodes. The research revealed that LHX2 knockout embryos exhibited similar hair follicle development abnormalities as those with reduced NF-κB signaling, including failure of E-cadherin suppression necessary for follicle down-growth. Additionally, TGFβ2 signaling was deficient in both NF-κB inhibited and LHX2 knockout embryos. Exogenous TGFβ2 was able to rescue hair follicle phenotypes in LHX2 knockout skin explants, suggesting a critical NF-κB-LHX2-TGFβ2 signaling axis in hair follicle morphogenesis.