Requirement of NF-κB/Rel for the development of hair follicles and other epidermal appendices
Open accessAbstract
NF-kappaB/Rel transcription factors and IkappaB kinases (IKK) are essential for inflammation and immune responses, but also for bone-morphogenesis, skin proliferation and differentiation. Determining their other functions has previously been impossible, owing to embryonic lethality of NF-kappaB/Rel or IKK-deficient animals. Using a gene targeting approach we have ubiquitously expressed an NF-kappaB super-repressor to investigate NF-kappaB functions in the adult. Mice with suppressed NF-kappaB revealed defective early morphogenesis of hair follicles, exocrine glands and teeth, identical to Eda (tabby) and Edar (downless) mutant mice. These affected epithelial appendices normally display high NF-kappaB activity, suppression of which resulted in increased apoptosis, indicating that NF-kappaB acts as a survival factor downstream of the tumor necrosis factor receptor family member EDAR. Furthermore, NF-kappaB is required for peripheral lymph node formation and macrophage function.
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The up-regulation of NF-κB and PI3K-Akt pathways is consistent with previous studies reporting that these genes are crucial for early hair follicle development and de novo regeneration of hair follicles.
“which is consistent with previous studies reporting that these genes are crucial for the early development of hair follicles and de novo regeneration of hair follicles (44, 45).”
From Reprogramming of three-dimensional microenvironments for in vitro hair follicle induction (2022) · cites this paper as [44]
Cites
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Self-citationEpidermal Development in Mammals: Key Regulators, Signals from Beneath, and Stem Cells
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Self-citationReprogramming of three-dimensional microenvironments for in vitro hair follicle induction
Kageyama, T., Shimizu, A., Anakama, R., Nakajima, R., Suzuki, K., Okubo, Y., & Fukuda, J. (2022) · Science Advances · doi:10.1126/sciadv.add4603 · Cited by 73 · see citing works
Overactivation of the NF‐κB pathway impairs molar enamel formation
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Self-citation
- Authors
- Schmidt-Ullrich, R., Aebischer, T., Hülsken, J., Birchmeier, W., Klemm, U., & Scheidereit, C.
- Affiliations
- Max-Delbrück-Center of Molecular Medicine, Robert-Rössle Straße 10, 13092 Berlin, Germany
- Max Planck Society (DE)
- Max Delbrück Center (DE)
- Venue
- Development
- Publisher
- The Company of Biologists
- Published
- 2001-10-01
- Volume
- 128
- Issue
- 19
- Pages
- 3843-3853
- ISSN
- 0950-1991 (ISSN-L)
- 1477-9129
- OpenAlex
- W2122723511
- Cited by
- 216
- References
- 1
- Citations by year
- 2026: 2 · 2025: 2 · 2024: 3 · 2023: 1 · 2022: 4 · 2021: 8 · 2020: 10 · 2019: 4 · 2018: 5 · 2017: 10 · 2016: 8 · 2015: 7 · 2014: 9 · 2013: 10 · 2012: 11
- FWCI
- 4.77
- Type
- journal article
- Language
- en
- Open access
- green
- infoscience.epfl.ch
- Locations
- Development (publishedVersion)
- PubMed (publishedVersion)
- Max Planck Institute for Plasma Physics (submittedVersion)
- Infoscience (Ecole Polytechnique Fédérale de Lausanne) (submittedVersion)
- MPG.PuRe (Max Planck Society) (submittedVersion)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › NF-κB Signaling Pathways
- Health Sciences › Medicine › Urology › Hair Growth and Disorders
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Skin and Cellular Biology Research
- Keywords
- IκB kinase, hair follicle morphogenesis, epidermal appendages, exocrine glands, tooth development, EDAR, apoptosis, macrophage function, gene targeting
- MeSH terms
- Animals, Deafness, Eccrine Glands, Epidermis, Exocrine Glands, Lymphatic System, Macrophages, Membrane Proteins, Mice, Inbred C57BL, Mice, Transgenic, Mutation, Otitis Media, Tooth, Signal Transduction, NF-kappa B, Apoptosis, Receptors, Tumor Necrosis Factor, Hair Follicle, Oncogene Proteins v-rel, I-kappa B Proteins, Hepatocytes, Mice, Ectodysplasins, Receptors, Ectodysplasin, Edar Receptor
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