ZBTB20 coordinates the proliferation-differentiation switch of incisor epithelial progenitor cells

The continuous growth of mouse incisors depends on the tightly coordinated proliferation and terminal differentiation of dental epithelial progenitors within the labial cervical loop (laCL). However, the molecular mechanisms governing the balance between these processes remain elusive. In this study, we identify the transcription factor ZBTB20 as a previously unreported regulator of the proliferation-differentiation switch. ZBTB20 is predominantly expressed in the undifferentiated progenitors within the mouse laCL during late embryonic and postnatal stages. Conditional deletion of Zbtb20 in dental epithelium resulted in delayed enamel mineralization, reduced enamel volume and excessive incisor growth. These defects were associated with enhanced proliferation and migration of transit-amplifying progenitor cells, as well as delayed pre-ameloblast and ameloblast differentiation. Integrated analysis of RNA sequencing and CUT&Tag revealed that ZBTB20 directly regulates the expression of key components of several signaling pathways, including ectodysplasin A, Notch and sonic hedgehog. Our findings highlight the essential role of ZBTB20 in orchestrating the interplay among multiple signaling pathways and provide new insights into the transcription network governing the proliferation-differentiation switch of dental epithelial progenitors during incisor development.