Involvement of Wnt, Eda, and Shh at Defined Stages of Sweat Gland Development

The study from 2014 investigated the mechanisms behind sweat gland development in mice, revealing a sequential involvement of the Wnt, Eda, and Shh signaling pathways. It was found that blocking canonical Wnt signaling in skin epithelium completely halted sweat gland formation and led to a significant decrease in the expression of Wnt, Eda, and Shh pathway genes. The Wnt antagonist Dkk4, which is induced by Wnt/β-catenin, was shown to suppress Wnt target genes and reduce the number of sweat glands when overexpressed. Although Wnt signaling was necessary for the initial induction of sweat gland pre-germs, Eda signaling was required for their further development, and without it, the Shh pathway was not activated. Finally, when Wnt and Eda signaling were functional but Shh was absent, sweat gland germ induction and duct formation occurred, but the formation of the secretory coil was unsuccessful. This study highlights a regulatory relay in sweat gland development, starting with Wnt/β-catenin and modulated by Dkk4, followed by Eda and then Shh pathways.