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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 ofEdamutant 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 byEDA—sweat gland induction and initial progression were accompanied byEda-dependent up-regulation of the Shh pathway. During the further development of sweat gland secretory portions,Foxa1andFoxi1, not at all expressed in hair follicles, were progressively up-regulated in WT but not in Tabby footpads. Upon completion of WT development,Shhdeclined to Tabby levels, butFoxfamily 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 toEda.

Requirement for Shh and Fox family genes at different stages in sweat gland development