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LHX2 is a direct NF-κB target gene that promotes primary hair follicle placode down-growth

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Item Type:Article
Title:LHX2 is a direct NF-κB target gene that promotes primary hair follicle placode down-growth
Creators Name:Tomann, P. and Paus, R. and Millar, S.E. and Scheidereit, C. and Schmidt-Ullrich, R.
Abstract:In the epidermis of mice lacking transcription factor nuclear factor-kappa B (NF-{kappa}B) activity, primary hair follicle (HF) pre-placode formation is initiated without progression to proper placodes. NF-{kappa}B modulates WNT and SHH signaling at early stages of HF development, but this does not fully account for the phenotypes observed upon NF-{kappa}B inhibition. To identify additional NF-{kappa}B target genes, we developed a novel method to isolate and transcriptionally profile primary HF placodes with active NF-{kappa}B signaling. In parallel, we compared gene expression at the same developmental stage in NF-{kappa}B-deficient embryos and controls. This uncovered novel NF-{kappa}B 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-{kappa}B target gene, loss of which replicates a subset of phenotypes seen in NF-{kappa}B-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 TGF{beta}2 signaling is impaired in NF-{kappa}B-deficient and Lhx2 knockout embryos and that exogenous TGF{beta}2 rescues the HF phenotypes in Lhx2 knockout skin explants, indicating that it operates downstream of LHX2. These findings identify a novel NF-{kappa}B/LHX2/TGF{beta}2 signaling axis that is crucial for primary HF morphogenesis, which may also function more broadly in development and disease.
Keywords:NF-{kappa}B, LHX2, Hair Follicle, TGF{beta}2, Cell Migration, E-Cadherin, EDA-A1, EDAR, Embryo, Placode, Stem Cell, Animals, Mice
Source:Development
ISSN:0950-1991
Publisher:Company of Biologists (U.K.)
Volume:143
Number:9
Page Range:1512-1522
Date:1 May 2016
Official Publication:https://doi.org/10.1242/dev.130898
PubMed:View item in PubMed

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