| First Author | Tomann P | Year | 2016 |
| Journal | Development | Volume | 143 |
| Issue | 9 | Pages | 1512-22 |
| PubMed ID | 26952977 | Mgi Jnum | J:235538 |
| Mgi Id | MGI:5796728 | Doi | 10.1242/dev.130898 |
| Citation | Tomann P, et al. (2016) Lhx2 is a direct NF-kappaB target gene that promotes primary hair follicle placode down-growth. Development 143(9):1512-22 |
| abstractText | In the epidermis of mice lacking transcription factor nuclear factor-kappa B (NF-kappaB) activity, primary hair follicle (HF) pre-placode formation is initiated without progression to proper placodes. NF-kappaB modulates WNT and SHH signaling at early stages of HF development, but this does not fully account for the phenotypes observed upon NF-kappaB inhibition. To identify additional NF-kappaB target genes, we developed a novel method to isolate and transcriptionally profile primary HF placodes with active NF-kappaB signaling. In parallel, we compared gene expression at the same developmental stage in NF-kappaB-deficient embryos and controls. This uncovered novel NF-kappaB target genes with potential roles in priming HF placodes for down-growth. Importantly, we identify Lhx2 (encoding a LIM/homeobox transcription factor) as a direct NF-kappaB target gene, loss of which replicates a subset of phenotypes seen in NF-kappaB-deficient embryos. Lhx2 and Tgfb2 knockout embryos exhibit very similar abnormalities in HF development, including failure of the E-cadherin suppression required for follicle down-growth. We show that TGFbeta2 signaling is impaired in NF-kappaB-deficient and Lhx2 knockout embryos and that exogenous TGFbeta2 rescues the HF phenotypes in Lhx2 knockout skin explants, indicating that it operates downstream of LHX2. These findings identify a novel NF-kappaB/LHX2/TGFbeta2 signaling axis that is crucial for primary HF morphogenesis, which may also function more broadly in development and disease. |
