The transcription factor nuclear factor-kappa B (NF-κB) plays an essential role in epidermal appendage induction and morphogenesis. In the epidermis of mice lacking NF-κB activity, initiation of primary hair follicle pre-placode formation is observed, but these primitive structures fail to proliferate and generate placodes. NF-κB signaling is known to modulate activity of WNT and SHH signaling at early stages of hair follicle development, but these roles do not fully account for the phenotypes observed when this pathway is blocked. To identify additional NF-κB target genes we developed a novel method to isolate and transcriptionally profile primary hair follicle placodes with active NF-κB signaling. In parallel, we compared gene expression at the same developmental stage in embryos with compromised NF-κB signaling, and wild type littermate controls. In addition to corroborating established NF-κB functions, these analyses uncovered novel NF-κB target genes with potential roles in priming hair follicle placodes for down-growth. Of particular interest, we identify the LIM/homeobox transcription factor LHX2 as a direct NF-κB target gene in this system, and show that loss of LHX2 replicates a subset of the phenotypes seen in embryos with reduced NF-κB signaling. LHX2 and TGFβ2 knockout embryos exhibit very similar abnormalities in hair follicle development, including failure of E-cadherin suppression that is required for follicle down-growth. Consistent with this, we find that TGFβ2 signaling is deficient in embryos with either inhibited NF-κB signaling or loss of LHX2. Furthermore, although TGFβ2 is not a direct LHX2 target gene, we find that exogenous TGFβ2 rescues the hair follicle phenotypes of LHX2 knockout skin explants, indicating that it operates downstream of LHX2. These findings identify a novel NF-κB-LHX2-TGFβ2 signaling axis that is critical for primary hair follicle morphogenesis and may function more broadly in development and disease.
LHX2 is a direct NF-κB target gene that promotes primary hair follicle placode down-growth
Currently Viewing Accepted Manuscript - Newer Version Available
Philip Tomann, Ralf Paus, Sarah E. Millar, Claus Scheidereit, Ruth Schmidt-Ullrich; LHX2 is a direct NF-κB target gene that promotes primary hair follicle placode down-growth. Development 2016; dev.130898. doi: https://doi.org/10.1242/dev.130898
Download citation file:
Advertisement
Call for papers: Uncovering Developmental Diversity
Development invites you to submit your latest research to our upcoming special issue: Uncovering Developmental Diversity. This issue will be coordinated by our academic Editor Cassandra Extavour (Harvard University, USA) alongside two Guest Editors: Liam Dolan (Gregor Mendel Institute of Molecular Plant Biology, Austria) and Karen Sears (University of California Los Angeles, USA).
Choose Development in 2024
In this Editorial, Development Editor-in-Chief James Briscoe and Executive Editor Katherine Brown explain how you support your community by publishing in Development and how the journal champions serious science, community connections and progressive publishing.
Journal Meeting: From Stem Cells to Human Development
Register now for the 2024 Development Journal Meeting From Stem Cells to Human Development. Early-bird registration deadline: 3 May. Abstract submission deadline: 21 June.
Pluripotency of a founding field: rebranding developmental biology
This collaborative Perspective, the result of a workshop held in 2023, proposes a set of community actions to increase the visibility of the developmental biology field. The authors make recommendations for new funding streams, frameworks for collaborations and mechanisms by which members of the community can promote themselves and their research.
Read & Publish Open Access publishing: what authors say
We have had great feedback from authors who have benefitted from our Read & Publish agreement with their institution and have been able to publish Open Access with us without paying an APC. Read what they had to say.