BMP-FGF Signaling Axis Mediates Wnt-Induced Epidermal Stratification in Developing Mammalian Skin
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Epidermal stratification of the mammalian skin requires proliferative basal progenitors to generate intermediate cells that separate from the basal layer and are replaced by post-mitotic cells. Although Wnt signaling has been implicated in this developmental process, the mechanism underlying Wnt-mediated regulation of basal progenitors remains elusive. Here we show that Wnt secreted from proliferative basal cells is not required for their differentiation. However, epidermal production of Wnts is essential for the formation of the spinous layer through modulation of a BMP-FGF signaling cascade in the dermis. The spinous layer defects caused by disruption of Wnt secretion can be restored by transgenically expressed Bmp4. Non-cell autonomous BMP4 promotes activation of FGF7 and FGF10 signaling, leading to an increase in proliferative basal cell population. Our findings identify an essential BMP-FGF signaling axis in the dermis that responds to the epidermal Wnts and feedbacks to regulate basal progenitors during epidermal stratification.
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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 [28]
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- Authors
- Zhu, X.-J., Liu, Y., Dai, Z.-M., Zhang, X., Yang, X., Li, Y., Qiu, M., Fu, J., Hsu, W., Chen, Y., & Zhang, Z.
- Affiliations
- Hangzhou Normal University (CN)
- University of Rochester Medicine (US)
- Tulane University (US)
- Corresponding author
- Zhang, Zunyi
- ORCID
- Venue
- PLoS Genetics
- Publisher
- Public Library of Science (PLoS)
- Published
- 2014-10-16
- Volume
- 10
- Issue
- 10
- Pages
- e1004687
- ISSN
- 1553-7390 (ISSN-L)
- 1553-7404
- PMC
- PMC4199507
- OpenAlex
- W2092198726
- Cited by
- 89
- References
- 64
- Citations by year
- 2026: 6 · 2025: 8 · 2024: 9 · 2023: 7 · 2022: 2 · 2021: 8 · 2020: 15 · 2019: 9 · 2018: 11 · 2017: 9 · 2016: 1 · 2015: 4
- FWCI
- 5.93
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Locations
- PLoS Genetics (publishedVersion, cc-by)
- Europe PMC (PubMed Central) (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Figshare (submittedVersion, cc-by)
- Funders
- Hangzhou Normal University
- National Cancer Institute (R01CA106308)
- National Institute of Dental and Craniofacial Research (R01DE015654)
- Topics
- Health Sciences › Medicine › Urology › Hair Growth and Disorders
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Wnt/β-catenin signaling in development and cancer
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Developmental Biology and Gene Regulation
- Keywords
- epidermal stratification, Wnt signaling, BMP4, FGF7, FGF10, basal progenitors, dermis, non-cell-autonomous signaling, skin development, Wnt secretion
- MeSH terms
- Epidermal Cells, Animals, Epidermis, Fibroblast Growth Factors, Mice, Transgenic, Phosphoproteins, Skin, Signal Transduction, Trans-Activators, Keratinocytes, Gene Expression Regulation, Developmental, Bone Morphogenetic Proteins, Receptors, G-Protein-Coupled, Intracellular Signaling Peptides and Proteins, Cell Proliferation, Fibroblast Growth Factor 7, Fibroblast Growth Factor 10, Smad1 Protein, Smad5 Protein, Smad8 Protein, Bone Morphogenetic Protein 4, Wnt Signaling Pathway
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