{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,16]],"date-time":"2026-10-16T06:39:26Z","timestamp":1792132766853,"version":"4.4.0"},"reference-count":79,"publisher":"The Company of Biologists","license":[{"start":{"date-parts":[[2016,11,1]],"date-time":"2016-11-01T00:00:00Z","timestamp":1477958400000},"content-version":"vor","delay-in-days":305,"URL":"http:\/\/www.biologists.com\/user-licence-1-1"}],"funder":[{"DOI":"10.13039\/501100001659","name":"Deutsche Forschungsgemeinschaft","doi-asserted-by":"publisher","award":["SCHM 855\/3-3"],"award-info":[{"award-number":["SCHM 855\/3-3"]}],"id":[{"id":"10.13039\/501100001659","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2016,1,1]]},"abstract":"<jats:p>The transcription factor nuclear factor-kappa B (NF-\u03baB) plays an essential role in epidermal appendage induction and morphogenesis. In the epidermis of mice lacking NF-\u03baB activity, initiation of primary hair follicle pre-placode formation is observed, but these primitive structures fail to proliferate and generate placodes. NF-\u03baB 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-\u03baB target genes we developed a novel method to isolate and transcriptionally profile primary hair follicle placodes with active NF-\u03baB signaling. In parallel, we compared gene expression at the same developmental stage in embryos with compromised NF-\u03baB signaling, and wild type littermate controls. In addition to corroborating established NF-\u03baB functions, these analyses uncovered novel NF-\u03baB 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-\u03baB target gene in this system, and show that loss of LHX2 replicates a subset of the phenotypes seen in embryos with reduced NF-\u03baB signaling. LHX2 and TGF\u03b22 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 TGF\u03b22 signaling is deficient in embryos with either inhibited NF-\u03baB signaling or loss of LHX2. Furthermore, although TGF\u03b22 is not a direct LHX2 target gene, we find that exogenous TGF\u03b22 rescues the hair follicle phenotypes of LHX2 knockout skin explants, indicating that it operates downstream of LHX2. These findings identify a novel NF-\u03baB-LHX2-TGF\u03b22 signaling axis that is critical for primary hair follicle morphogenesis and may function more broadly in development and disease.<\/jats:p>","DOI":"10.1242\/dev.130898","type":"journal-article","created":{"date-parts":[[2016,3,8]],"date-time":"2016-03-08T02:40:01Z","timestamp":1457404801000},"source":"Crossref","is-referenced-by-count":35,"title":["LHX2 is a direct NF-\u03baB target gene that promotes primary hair follicle placode down-growth"],"prefix":"10.1242","author":[{"given":"Philip","family":"Tomann","sequence":"first","affiliation":[{"name":"Dept. Signal Transduction in Tumor Cells, Max-Delbr\u00fcck-Center (MDC) for Molecular Medicine, 13092 Berlin, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ralf","family":"Paus","sequence":"additional","affiliation":[{"name":"Department of Dermatology, University of M\u00fcnster, 48149 M\u00fcnster, Germany & Centre for Dermatology Research, Institute of Inflammation and Repair, University of Manchester, Manchester, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sarah E.","family":"Millar","sequence":"additional","affiliation":[{"name":"Departments of Dermatology and Cell and Developmental Biology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Claus","family":"Scheidereit","sequence":"additional","affiliation":[{"name":"Dept. Signal Transduction in Tumor Cells, Max-Delbr\u00fcck-Center (MDC) for Molecular Medicine, 13092 Berlin, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ruth","family":"Schmidt-Ullrich","sequence":"additional","affiliation":[{"name":"Dept. Signal Transduction in Tumor Cells, Max-Delbr\u00fcck-Center (MDC) for Molecular Medicine, 13092 Berlin, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"237","reference":[{"key":"2021042608492912300_DEV130898C1","doi-asserted-by":"publisher","first-page":"588","DOI":"10.1016\/j.devcel.2014.02.003","article-title":"Directional cell migration, but not proliferation, drives hair placode morphogenesis","volume":"28","author":"Ahtiainen","year":"2014","journal-title":"Dev. 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