Involvement of Wnt, Eda and Shh at defined stages of sweat gland development
Open accessAbstract
To maintain body temperature, sweat glands develop from embryonic ectoderm by a poorly defined mechanism. We demonstrate a temporal cascade of regulation during mouse sweat gland formation. Sweat gland induction failed completely when canonical Wnt signaling was blocked in skin epithelium, and was accompanied by sharp downregulation of downstream Wnt, Eda and Shh pathway genes. The Wnt antagonist Dkk4 appeared to inhibit this induction: Dkk4 was sharply downregulated in β-catenin-ablated mice, indicating that it is induced by Wnt/β-catenin; however, its overexpression repressed Wnt target genes and significantly reduced gland numbers. Eda signaling succeeded Wnt. Wnt signaling was still active and nascent sweat gland pre-germs were still seen in Eda-null mice, but the pre-germs failed to develop further and the downstream Shh pathway was not activated. When Wnt and Eda were intact but Shh was ablated, germ induction and subsequent duct formation occurred normally, but the final stage of secretory coil formation failed. Thus, sweat gland development shows a relay of regulatory steps initiated by Wnt/β-catenin – itself modulated by Dkk4 – with subsequent participation of Eda and Shh pathways.
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EDA signaling has a key role in SwG initiation and development.
“Ectodysplasin‐A (EDA) signaling has a key role in SwG initiation and development.[ 13 , 14 ]”
From Sweat Gland Organoids Originating from Reprogrammed Epidermal Keratinocytes Functionally Recapitulated Damaged Skin (2021) · cites this paper as [14]
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- Authors
- Cui, C.-Y., Yin, M., Sima, J., Childress, V., Michel, M., Piao, Y., & Schlessinger, D.
- Affiliations
- National Institutes of Health (US)
- Corresponding author
- Cui, Chang-Yi
- Venue
- Development
- Publisher
- The Company of Biologists
- Published
- 2014-10-01
- Volume
- 141
- Issue
- 19
- Pages
- 3752-3760
- ISSN
- 0950-1991 (ISSN-L)
- 1477-9129
- PMC
- PMC4197578
- OpenAlex
- W1970772787
- Cited by
- 80
- References
- 51
- Citations by year
- 2026: 11 · 2025: 9 · 2024: 7 · 2023: 11 · 2022: 7 · 2021: 5 · 2020: 6 · 2019: 7 · 2018: 2 · 2017: 6 · 2016: 5 · 2015: 3
- FWCI
- 5.93
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Development (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- HighWire Press Open Archive (submittedVersion)
- Funders
- National Institutes of Health
- 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
- sweat gland development, Wnt/β-catenin signaling, Sonic hedgehog signaling, DKK4, skin epithelium, mouse embryo
- MeSH terms
- Animals, Fluorescent Antibody Technique, Galactosides, Indoles, Mice, Transgenic, Sweat Glands, In Situ Hybridization, DNA Primers, Gene Expression Regulation, Developmental, Gene Expression Profiling, Intercellular Signaling Peptides and Proteins, Wnt Proteins, beta Catenin, Mice, Ectodysplasins, Hedgehog Proteins, Wnt Signaling Pathway, Real-Time Polymerase Chain Reaction
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