KGF and EGF signalling block hair follicle induction and promote interfollicular epidermal fate in developing mouse skin
Open accessAbstract
A key initial event in hair follicle morphogenesis is the localised thickening of the skin epithelium to form a placode, partitioning future hair follicle epithelium from interfollicular epidermis. Although many developmental signalling pathways are implicated in follicle morphogenesis,the role of epidermal growth factor (EGF) and keratinocyte growth factor (KGF,also known as FGF7) receptors are not defined. EGF receptor (EGFR) ligands have previously been shown to inhibit developing hair follicles; however, the underlying mechanisms have not been characterised. Here we show that receptors for EGF and KGF undergo marked downregulation in hair follicle placodes from multiple body sites, whereas the expression of endogenous ligands persist throughout hair follicle initiation. Using embryonic skin organ culture, we show that when skin from the sites of primary pelage and whisker follicle development is exposed to increased levels of two ectopic EGFR ligands (HBEGF and amphiregulin) and the FGFR2(IIIb) receptor ligand KGF, follicle formation is inhibited in a time- and dose-dependent manner. We then used downstream molecular markers and microarray profiling to provide evidence that, in response to KGF and EGF signalling, epidermal differentiation is promoted at the expense of hair follicle fate. We propose that hair follicle initiation in placodes requires downregulation of the two pathways in question, both of which are crucial for the ongoing development of the interfollicular epidermis. We have also uncovered a previously unrecognised role for KGF signalling in the formation of hair follicles in the mouse.
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Presumptive dermal cells expressed FGF7 (Keratinocyte Growth Factor), which may be a key driver of epidermal stratification in this system.
“Presumptive dermal cells expressed FGF7 (Keratinocyte Growth Factor), which may be a key driver of epidermal stratification in this system (Extended Data Fig. 6f)28,29.”
From Hair-bearing human skin generated entirely from pluripotent stem cells (2020) · cites this paper as [29]
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- Authors
- Richardson, G. D., Bazzi, H., Fantauzzo, K. A., Waters, J. M., Crawford, H., Hynd, P., Christiano, A. M., & Jahoda, C. A. B.
- Affiliations
- Durham University (GB)
- Columbia University (US)
- School of Animal and Veterinary Science, The University of Adelaide,Roseworthy, South Australia 5371, Australia.
- Corresponding author
- Jahoda, Colin A. B.
- ORCID
- Venue
- Development
- Publisher
- The Company of Biologists
- Published
- 2009-07-01
- Volume
- 136
- Issue
- 13
- Pages
- 2153-2164
- ISSN
- 0950-1991 (ISSN-L)
- 1477-9129
- PMC
- PMC2729337
- OpenAlex
- W2071313744
- Cited by
- 103
- References
- 72
- Citations by year
- 2026: 2 · 2025: 3 · 2024: 10 · 2023: 8 · 2022: 6 · 2021: 8 · 2020: 8 · 2019: 4 · 2018: 3 · 2017: 2 · 2016: 7 · 2015: 7 · 2014: 9 · 2013: 9 · 2012: 8
- FWCI
- 6.65
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Development (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Adelaide Research & Scholarship (AR&S) (University of Adelaide) (submittedVersion)
- Durham Research Online (Durham University) (submittedVersion)
- Durham Research Online (Durham University) (submittedVersion, cc-by)
- Newcastle University ePrints (Newcastle Univesity)
- Funders
- Biotechnology and Biological Sciences Research Council (G18988)
- Topics
- Health Sciences › Medicine › Urology › Hair Growth and Disorders
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › dental development and anomalies
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Skin and Cellular Biology Research
- Keywords
- hair follicle induction, keratinocyte growth factor, FGF7, epidermal growth factor receptor, EGF signaling, interfollicular epidermis, epidermal differentiation, HB-EGF, amphiregulin, FGFR2-IIIb
- MeSH terms
- Zinc Finger Protein GLI1, Epidermal Cells, Animals, Cell Differentiation, Enzyme Inhibitors, Epidermal Growth Factor, Epidermis, Glycoproteins, Mice, Inbred C57BL, Morphogenesis, Quinazolines, Skin, Vibrissae, Signal Transduction, Oncogene Proteins, Trans-Activators, Cadherins, Hair Follicle, Hyaluronan Receptors, Tyrphostins, Intercellular Signaling Peptides and Proteins, Tissue Culture Techniques, Wnt Proteins, beta Catenin, Mice, Receptor, Fibroblast Growth Factor, Type 2, Fibroblast Growth Factor 7, Fibroblast Growth Factor 10, Syndecan-1, Hedgehog Proteins, ErbB Receptors, EGF Family of Proteins, Heparin-binding EGF-like Growth Factor, Amphiregulin
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