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Identification of Eda targets during Meibomian gland development

ABSTRACT: Eda signaling plays critical role for Meibomian gland dvelopment, however, the crosstalk of Eda with other signaling is largly unknown. By comparing expreession profilings between wild-type and Eda mutant Tabby eyelids, we identified Dkk4 and Lrp6 highly expressed during mouse Meibomian gland development.

ORGANISM(S): Mus musculus

PROVIDER: GSE87742 | GEO | 2016/12/13

SECONDARY ACCESSION(S): PRJNA347323

REPOSITORIES: GEO

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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.

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