Cascade regulation of sweat gland development by Wnt, Eda and Shh pathways
Ontology highlight
ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE50863 | GEO | 2014/08/20
SECONDARY ACCESSION(S): PRJNA219187
REPOSITORIES: GEO
Similar Datasets
Project description:This SuperSeries is composed of the SubSeries listed below. Refer to individual Series
2014-08-20 | E-GEOD-50863 | biostudies-arrayexpress
Project description:Millions of sweat glands required to maintain body temperature develop from embryonic ectoderm by a poorly defined mechanism. We present evidence for temporal cascade regulation of sweat gland development by Wnt, Eda and Shh pathways. The first stage, sweat gland induction, failed completely when Wnt/β-catenin signaling was blocked in skin epithelium, accompanied by sharp downregulation of Wnt, Eda and Shh pathway genes. In a meta-layer of regulation, Wnt antagonist Dkk4 appeared to operate on sweat gland induction in a negative feedback loop: Dkk4 was itself sharply downregulated in β-catenin-ablated mice, whereas its over-expression repressed Wnt target genes and significantly reduced gland numbers. Eda signaling succeeded Wnt, and activated downstream Shh pathway. Thus, in absence of Eda, Wnt pathway was still active and initial sweat gland pre-germs were seen but failed to develop germs, and dwonstream Shh pathway was repressed. When both Wnt and Eda were intact but Shh was ablated, early stage induction and subsequent duct formation occurred normally, but the final stage formation of secretory coil failed. Thus, sweat gland development shows a relay of regulatory steps, initiated by Wnt/β-catenin -- itself modulated by Dkk4 -- with subsequent tandem action of Eda and Shh pathways.
2014-08-20 | GSE50862 | GEO
Project description:Millions of sweat glands required to maintain body temperature develop from embryonic ectoderm by a poorly defined mechanism. We present evidence for temporal cascade regulation of sweat gland development by Wnt, Eda and Shh pathways. The first stage, sweat gland induction, failed completely when Wnt/?-catenin signaling was blocked in skin epithelium, accompanied by sharp downregulation of Wnt, Eda and Shh pathway genes. In a meta-layer of regulation, Wnt antagonist Dkk4 appeared to operate on sweat gland induction in a negative feedback loop: Dkk4 was itself sharply downregulated in ?-catenin-ablated mice, whereas its over-expression repressed Wnt target genes and significantly reduced gland numbers. Eda signaling succeeded Wnt, and activated downstream Shh pathway. Thus, in absence of Eda, Wnt pathway was still active and initial sweat gland pre-germs were seen but failed to develop germs, and dwonstream Shh pathway was repressed. When both Wnt and Eda were intact but Shh was ablated, early stage induction and subsequent duct formation occurred normally, but the final stage formation of secretory coil failed. Thus, sweat gland development shows a relay of regulatory steps, initiated by Wnt/?-catenin -- itself modulated by Dkk4 -- with subsequent tandem action of Eda and Shh pathways. Compared expression changes between WT and skin specific Dkk4 transgenic footpads at 2 developmental time points, E15.5 and E16.5. Data were duplicated with 2 sets of samples.
2014-08-20 | E-GEOD-50862 | biostudies-arrayexpress
Project description:Millions of sweat glands required to maintain body temperature develop from embryonic ectoderm by a poorly defined mechanism. We present evidence for temporal cascade regulation of sweat gland development by Wnt, Eda and Shh pathways. The first stage, sweat gland induction, failed completely when Wnt/β-catenin signaling was blocked in skin epithelium, accompanied by sharp downregulation of Wnt, Eda and Shh pathway genes. In a meta-layer of regulation, Wnt antagonist Dkk4 appeared to operate on sweat gland induction in a negative feedback loop: Dkk4 was itself sharply downregulated in β-catenin-ablated mice, whereas its over-expression repressed Wnt target genes and significantly reduced gland numbers. Eda signaling succeeded Wnt, and activated downstream Shh pathway. Thus, in absence of Eda, Wnt pathway was still active and initial sweat gland pre-germs were seen but failed to develop germs, and dwonstream Shh pathway was repressed. When both Wnt and Eda were intact but Shh was ablated, early stage induction and subsequent duct formation occurred normally, but the final stage formation of secretory coil failed. Thus, sweat gland development shows a relay of regulatory steps, initiated by Wnt/β-catenin -- itself modulated by Dkk4 -- with subsequent tandem action of Eda and Shh pathways.
2014-08-20 | GSE50859 | GEO
Project description:Millions of sweat glands required to maintain body temperature develop from embryonic ectoderm by a poorly defined mechanism. We present evidence for temporal cascade regulation of sweat gland development by Wnt, Eda and Shh pathways. The first stage, sweat gland induction, failed completely when Wnt/β-catenin signaling was blocked in skin epithelium, accompanied by sharp downregulation of Wnt, Eda and Shh pathway genes. In a meta-layer of regulation, Wnt antagonist Dkk4 appeared to operate on sweat gland induction in a negative feedback loop: Dkk4 was itself sharply downregulated in β-catenin-ablated mice, whereas its over-expression repressed Wnt target genes and significantly reduced gland numbers. Eda signaling succeeded Wnt, and activated downstream Shh pathway. Thus, in absence of Eda, Wnt pathway was still active and initial sweat gland pre-germs were seen but failed to develop germs, and dwonstream Shh pathway was repressed. When both Wnt and Eda were intact but Shh was ablated, early stage induction and subsequent duct formation occurred normally, but the final stage formation of secretory coil failed. Thus, sweat gland development shows a relay of regulatory steps, initiated by Wnt/β-catenin -- itself modulated by Dkk4 -- with subsequent tandem action of Eda and Shh pathways. Compared expression changes between wild type and skin specific beta-catenin knockout footpads at 3 developmental time points, E15.5, E16.5 and E17.5. Data were duplicated with 2 sets of samples.
2014-08-20 | E-GEOD-50859 | biostudies-arrayexpress
Project description: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.
| S-EPMC4197578 | biostudies-literature
Project description:The Sonic hedgehog (Shh) signaling pathway regulates developmental, homeostatic, and repair processes throughout the body. In the skin, touch domes develop in tandem with primary hair follicles and contain sensory Merkel cells. The developmental signaling requirements for touch dome specification are largely unknown. We found dermal Wnt signaling and subsequent epidermal Eda/Edar signaling promoted Merkel cell morphogenesis by inducing Shh expression in early follicles. Lineage-specific gene deletions revealed intraepithelial Shh signaling was necessary for Merkel cell specification. Additionally, a Shh signaling agonist was sufficient to rescue Merkel cell differentiation in Edar-deficient skin. Moreover, Merkel cells formed in Fgf20 mutant skin where primary hair formation was defective but Shh production was preserved. Although developmentally associated with hair follicles, fate mapping demonstrated Merkel cells primarily originated outside the hair follicle lineage. These findings suggest that touch dome development requires Wnt-dependent mesenchymal signals to establish reciprocal signaling within the developing ectoderm, including Eda signaling to primary hair placodes and ultimately Shh signaling from primary follicles to extrafollicular Merkel cell progenitors. Shh signaling often demonstrates pleiotropic effects within a structure over time. In postnatal skin, Shh is known to regulate the self-renewal, but not the differentiation, of touch dome stem cells. Our findings relate the varied effects of Shh in the touch dome to the ligand source, with locally produced Shh acting as a morphogen essential for lineage specification during development and neural Shh regulating postnatal touch dome stem cell maintenance.
| S-EPMC4944988 | biostudies-literature
Project description:EDA signaling is important in skin appendage initiation. Its possible involvement in appendage subtype determination and postinduction stage appendage development, however, has not been studied systematically. To address these issues we manipulated Eda-A1 transgene expression in a tetracycline-regulated conditional mouse model, where the transgene is the only source of active ectodysplasin (Eda). We find that Eda-A1 restores sweat glands and all hair subtypes in Tabby, but each requires its action at an idiosyncratic time of development: by E17 for guard, by E19 for awl, and starting at E18 for zigzag/auchen hair. Guard and awl hairs were indistinguishable from their wild-type counterparts; but restored zigzag and auchen hairs, although recognizable, were somewhat smaller and lacked characteristic bends. Notably, secondary hair follicle formation of awl, auchen, and zigzag hairs required higher Eda-A1 expression level than did guard hair or sweat glands. Furthermore, Eda-A1 expression is required until the early dermal papilla stage for guard hair germs to make follicles, but is dispensable for their maturation. Similarly, sweat gland pegs require Eda-A1 at an early stage to form mature glands. Thus we infer that EDA signaling is needed for the determination and development of various skin appendages at spatiotemporally restricted intervals.
| S-EPMC5155335 | biostudies-literature
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, with wild-type (WT) mice. We inferred developmental stages and critical genes based on observations at seven time points spanning embryonic, postnatal and adult life. In WT 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 completed 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 were 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 WT but not in Tabby footpads. Upon completion of WT 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 down-stream regulation of gene action, possibly by a signaling cascade, in response to Eda.
| S-EPMC2671986 | biostudies-literature
Project description:Sweat gland (SG) cells forming SG tubule-like structures in 3D culture, this is one of the most important methods to identify the biological function of SG cells and stem cells-derived SG-like cells, but also the important way on research of SG regeneration in vitro. In this study, we seeded human fibroblasts and SG cells in gels and used immunohistochemistry to confirm whether SG tubule-like structures formed. Fibroblasts are necessary factor in the process of SG cells maturation and forming SG's secretory region in 3D culture. Further experimentation revealed that Sonic hedgehog (Shh) was secreted by fibroblasts within the 3D culture. By adding Shh protein to 3D culture, there had more SG tubule-like structures formed. These results suggest that Shh is an important factor during the process of forming SG tubule-like structures in 3D cultures, and adding Shh recommbinant protein could promote SG cell maturation and enhance the efficiency of structure formation.
| S-EPMC4882370 | biostudies-literature