Figure 8.
Schematic of hypothesized model for Sufu-dependent balance of Gli repressors and activators in regulating calvarial bone development. In wild-type calvarial mesenchymal cells, Sufu is required for maintaining the balance of Gli2 and Gli3 activity (A). Calvarial mesenchymal cells in Sufufx/fx;Wnt1-Cre mutant cannot undergo normal condensation and osteogenic differentiation due to the deletion of Sufu that leads to a decrease of Gli repressors and an increase of Hh signaling activity (B). This leads to activation of downstream Jag1/Notch signaling and inhibition of BMP signaling, respectively, resulting in dysregulation of osteogenic markers Runx2 and Osterix. Simultaneous removal of Sufu and Gli2 can compromise Hh activity by rebalancing the Gli repressors and full-length activators, which promotes the proliferation and differentiation of osteoprogenitor cells (C). The regulatory relationships shown in dashed lines are drawn according to previous studies from other researchers (41, 44, 45, 51–53).