Involvement of Wnt, Eda and Shh at defined stages of sweat gland development
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 a...
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| Published in: | Development (Cambridge) Vol. 141; no. 19; p. 3752 |
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| Main Authors: | , , , , , , |
| Format: | Journal Article |
| Language: | English |
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England
01.10.2014
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| ISSN: | 1477-9129, 1477-9129 |
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| Abstract | 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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| AbstractList | 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.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. 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. |
| Author | Piao, Yulan Yin, Mingzhu Cui, Chang-Yi Sima, Jian Michel, Marc Schlessinger, David Childress, Victoria |
| Author_xml | – sequence: 1 givenname: Chang-Yi surname: Cui fullname: Cui, Chang-Yi email: cuic@mail.nih.gov organization: Laboratory of Genetics, National Institute on Aging, National Institutes of Health, Baltimore, MD 21224, USA cuic@mail.nih.gov – sequence: 2 givenname: Mingzhu surname: Yin fullname: Yin, Mingzhu organization: Laboratory of Genetics, National Institute on Aging, National Institutes of Health, Baltimore, MD 21224, USA – sequence: 3 givenname: Jian surname: Sima fullname: Sima, Jian organization: Laboratory of Genetics, National Institute on Aging, National Institutes of Health, Baltimore, MD 21224, USA – sequence: 4 givenname: Victoria surname: Childress fullname: Childress, Victoria organization: Laboratory of Genetics, National Institute on Aging, National Institutes of Health, Baltimore, MD 21224, USA – sequence: 5 givenname: Marc surname: Michel fullname: Michel, Marc organization: Laboratory of Genetics, National Institute on Aging, National Institutes of Health, Baltimore, MD 21224, USA – sequence: 6 givenname: Yulan surname: Piao fullname: Piao, Yulan organization: Laboratory of Genetics, National Institute on Aging, National Institutes of Health, Baltimore, MD 21224, USA – sequence: 7 givenname: David surname: Schlessinger fullname: Schlessinger, David organization: Laboratory of Genetics, National Institute on Aging, National Institutes of Health, Baltimore, MD 21224, USA |
| BackLink | https://www.ncbi.nlm.nih.gov/pubmed/25249463$$D View this record in MEDLINE/PubMed |
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| Keywords | Hyperhidrosis Mouse Exocrine gland Hair follicle Heatstroke Ectodermal dysplasia Skin appendage |
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| SubjectTerms | Animals beta Catenin - deficiency DNA Primers - genetics Ectodysplasins - metabolism Fluorescent Antibody Technique Galactosides Gene Expression Profiling Gene Expression Regulation, Developmental - genetics Gene Expression Regulation, Developmental - physiology Hedgehog Proteins - metabolism In Situ Hybridization Indoles Intercellular Signaling Peptides and Proteins - genetics Intercellular Signaling Peptides and Proteins - metabolism Mice Mice, Transgenic Real-Time Polymerase Chain Reaction Sweat Glands - embryology Sweat Glands - metabolism Wnt Proteins - metabolism Wnt Signaling Pathway - physiology |
| Title | Involvement of Wnt, Eda and Shh at defined stages of sweat gland development |
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