Lhx2 is a direct NF-κB target gene that promotes primary hair follicle placode down-growth.
Development
; 143(9): 1512-22, 2016 05 01.
Article
em En
| MEDLINE
| ID: mdl-26952977
ABSTRACT
In the epidermis of mice lacking transcription factor nuclear factor-kappa 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 down-growth. 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 TGFß2 signaling is impaired in NF-κB-deficient and Lhx2 knockout embryos and that exogenous TGFß2 rescues the HF phenotypes in Lhx2 knockout skin explants, indicating that it operates downstream of LHX2. These findings identify a novel NF-κB/LHX2/TGFß2 signaling axis that is crucial for primary HF morphogenesis, which may also function more broadly in development and disease.
Palavras-chave
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Fatores de Transcrição
/
Regulação da Expressão Gênica no Desenvolvimento
/
Folículo Piloso
/
Organogênese
/
Fator de Transcrição RelA
/
Fator de Crescimento Transformador beta2
/
Proteínas com Homeodomínio LIM
Idioma:
En
Ano de publicação:
2016
Tipo de documento:
Article