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Using Confocal Analysis of Xenopus laevis to Investigate Modulators of Wnt and Shh Morphogen Gradients
Published on: December 14, 2015
Involvement of Wnt, Eda and Shh at defined stages of sweat gland development
Chang-Yi Cui1, Mingzhu Yin2, Jian Sima2
1Laboratory of Genetics, National Institute on Aging, National Institutes of Health, Baltimore, MD 21224, USA cuic@mail.nih.gov.
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.
Insights
Sweat gland development in mice relies on a sequential signaling pathway. Wnt/β-catenin initiates the process, followed by Eda and Shh signaling, which are crucial for proper gland formation and function.
Area of Science:
- Developmental Biology
- Dermatology
- Molecular Biology
Background:
- Sweat glands are essential for thermoregulation.
- The precise molecular mechanisms governing sweat gland development from embryonic ectoderm are not fully understood.
Purpose of the Study:
- To elucidate the temporal cascade of signaling pathways involved in mouse sweat gland formation.
- To identify the roles of Wnt, Eda, and Shh signaling in this developmental process.
Main Methods:
- Genetic manipulation in mice to block or ablate specific signaling pathways (Wnt/β-catenin, Eda, Shh).
- Analysis of gene expression and developmental phenotypes.
- Overexpression studies of Wnt antagonist Dkk4.
Main Results:
- Canonical Wnt signaling is essential for initial sweat gland induction; blocking it halts development and downregulates downstream pathways.
- Eda signaling acts downstream of Wnt, with Eda-null mice showing arrested pre-germ development.
- Shh signaling is required for secretory coil formation, as ablation prevents this final stage.
Conclusions:
- Mouse sweat gland development follows a precise temporal relay of Wnt/β-catenin, Eda, and Shh signaling pathways.
- Dkk4 modulates Wnt/β-catenin signaling, impacting gland development.
- This study reveals a stepwise regulatory mechanism for sweat gland formation.
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