Abstract
In the epidermis of mice lacking transcription factor nuclear factorkappa B (NF-κB) activity, primary hair follicle (HF) pre-placode formation is initiated without progression to proper placodes. NF-κB modulates WNT and SHH signaling at early stages of HF development, but this does not fully account for the phenotypes observed upon NF-κB inhibition. To identify additional NF-κB target genes, we developed a novel method to isolate and transcriptionally profile primary HF placodes with active NF-κB signaling. In parallel, we compared gene expression at the same developmental stage in NF-κB-deficient embryos and controls. This uncovered novel NF-κB target genes with potential roles in priming HF placodes for downgrowth. Importantly, we identify Lhx2 (encoding a LIM/homeobox transcription factor) as a direct NF-κB target gene, loss of which replicates a subset of phenotypes seen in NF-κB-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 TGFβ2 signaling is impaired in NF-κB-deficient and Lhx2 knockout embryos and that exogenous TGFβ2 rescues the HF phenotypes in Lhx2 knockout skin explants, indicating that it operates downstream of LHX2. These findings identify a novel NF-κB/LHX2/TGFβ2 signaling axis that is crucial for primary HF morphogenesis, which may also function more broadly in development and disease.
Original language | English (US) |
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Pages (from-to) | 1512-1522 |
Number of pages | 11 |
Journal | Development (Cambridge) |
Volume | 143 |
Issue number | 9 |
DOIs | |
State | Published - May 2016 |
Externally published | Yes |
Keywords
- Cell migration
- E-cadherin
- EDA-A1
- EDAR
- Embryo
- Hair follicle
- LHX2
- Mouse
- NF-κB
- Placode
- Stem cell
- TGFβ2
ASJC Scopus subject areas
- Molecular Biology
- Developmental Biology