Lhx2 is a direct NF-κB target gene that promotes primary hair follicle placode down-growth

Philip Tomann, Ralf Paus, Sarah E. Millar, Claus Scheidereit, Ruth Schmidt-Ullrich

Research output: Contribution to journalArticle

10 Scopus citations

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 languageEnglish (US)
Pages (from-to)1512-1522
Number of pages11
JournalDevelopment (Cambridge)
Volume143
Issue number9
DOIs
StatePublished - May 2016

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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

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