Dataset Information

Involvement of Wnt, Eda and Shh at defined stages of sweat gland development.

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 ?-catenin-ablated mice, indicating that it is induced by Wnt/?-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/?-catenin - itself modulated by Dkk4 - with subsequent participation of Eda and Shh pathways.

SUBMITTER: Cui CY

PROVIDER: S-EPMC4197578 | biostudies-literature | 2014 Oct

REPOSITORIES: biostudies-literature

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Involvement of Wnt, Eda and Shh at defined stages of sweat gland development.

Cui Chang-Yi CY Yin Mingzhu M Sima Jian J Childress Victoria V Michel Marc M Piao Yulan Y Schlessinger David D

Development (Cambridge, England) 20141001 19

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, i ...[more]

PMID: 25249463

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Project description:Sweat glands play a fundamental role in thermal regulation in man, but the molecular mechanism of their development remains unknown. To initiate analyses, we compared the model of Eda mutant Tabby mice, in which sweat glands were not formed, to wild-type mice. We inferred developmental stages and critical genes based on observations at 7 time points spanning embryonic, postnatal and adult life. In wild-type footpads, sweat gland germs were detected at E17.5. The coiling of secretory portions started at postnatal day 1 (P1), and sweat gland formation was essentially complete by P5. Consistent with a controlled morphological progression, expression profiling revealed stage-specific gene expression changes. Similar to the development of hair follicles the other major skin appendage controlled by EDA sweat gland induction and initial progression was accompanied by Eda-dependent up-regulation of the Shh pathway. During the further development of sweat gland secretory portions, Foxa1 and Foxi1, not at all expressed in hair follicles, were progressively up-regulated in wild-type but not in Tabby footpads. Upon completion of wild-type development, Shh declined to Tabby levels, but Fox family genes remained at elevated levels in mature sweat glands. The results provide a framework for the further analysis of phased downstream regulation of gene action, possibly by a signaling cascade, in response to Eda. This SuperSeries is composed of the following subset Series: GSE14870: Requirement for Shh and Fox family genes at different stages in sweat gland development (E15.5) GSE14871: Requirement for Shh and Fox family genes at different stages in sweat gland development (E16.5) GSE14872: Requirement for Shh and Fox family genes at different stages in sweat gland development (E17.5) GSE14873: Requirement for Shh and Fox family genes at different stages in sweat gland development (P1) GSE14874: Requirement for Shh and Fox family genes at different stages in sweat gland development (P3) GSE14876: Requirement for Shh and Fox family genes at different stages in sweat gland development (P5) GSE14877: Requirement for Shh and Fox family genes at different stages in sweat gland development (Adult) To define target genes of Eda during sweat gland development, we carried out microarray experiments with mouse footpads that from 7 developmental time points including E15.5, E16.5, E17.5, P1, P3, P5 and 8 weeks of wild-type and Tabby mice. Refer to individual Series

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Involvement of Wnt, Eda and Shh at defined stages of sweat gland development.

Publications

Involvement of Wnt, Eda and Shh at defined stages of sweat gland development.

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