Initiation and subsequent growth of the mammalian tooth depends on distinct populations of epithelial and mesenchymal stem cells located in the labial cervical loop (LaCL) and the neurovascular bundle, respectively. In rodents, Sox2 marks the dental epithelial stem cells (DESCs) and has been shown to be an important regulator of tooth development, but the molecular mechanism by which this occurs has not been determined. In this issue (p. 4115), Brad Amendt and colleagues uncover a Pitx2/Sox2/Lef-1 network that controls the epithelial stem cell niche in the continuously erupting rodent incisor. The authors demonstrate that Sox2 is necessary for the maintenance of the stem cell niche, as inactivation of Sox2 leads to lower incisor arrest, as well as abnormalities in the upper incisor and molar teeth. Conditional overexpression of Lef-1 can partially rescue the Sox2-related defect in incisor growth, possibly owing to increased cell proliferation at embryonic stages and the formation of a new compartment of stem cells in the LaCL. The authors also provide evidence for physical interaction between Pitx2 and Sox2, and show how both factors are core components of the Pitx2/Sox2/Lef-1 network. Together, these findings represent a significant milestone in our understanding of the transcriptional control that defines dental stem cell development and differentiation.

• © 2016. Published by The Company of Biologists Ltd