BMP-SHH signaling network controls epithelial stem cell fate via regulation of its niche in the developing tooth

[Display omitted] •Sox2+ epithelial stem cells exist transiently during molar development•Loss of Smad4 results in ectopic SHH-Gli1 signaling and maintenance of Sox2+ cells•BMP-Smad4-SHH signaling regulates epithelial stem cell maintenance in teeth•SHH-Gli1 activity provides a niche for dental epithelial stem cell maintenance During embryogenesis, ectodermal stem cells adopt different fates and form diverse ectodermal organs, such as teeth, hair follicles, mammary glands and salivary glands. Interestingly, these ectodermal organs differ in their tissue homeostasis, which leads to differential abilities for continuous growth postnatally. Mouse molars lose the ability to grow continuously whereas incisors retain this ability. In this study, we found that a BMP-Smad4-SHH-Gli1 signaling network may provide a niche supporting transient Sox2+ dental epithelial stem cells in mouse molars. This mechanism also plays a role in continuously growing mouse incisors. The differential fate of epithelial stem cells in mouse molars and incisors is controlled by this BMP/SHH signaling network, which partially accounts for the different postnatal growth potential of molars and incisors. Collectively, our study highlights the importance of crosstalk between two signaling pathways, BMP and SHH, in regulating the fate of epithelial stem cells during organogenesis.