The shape of an individual tooth crown is primarily determined by the number and arrangement of its cusps, i.e., cusp patterning. Enamel knots that appear in the enamel organ during tooth morphogenesis have been suggested to play important roles in cusp patterning. Animal model studies have shown that the Hippo pathway effector Yap has a critical function in tooth morphogenesis. However, the role of the Hippo pathway/Yap in cusp patterning has not been well documented and its specific roles in tooth morphogenesis remain unclear. Here, we provide evidence that Yap is a key mediator in tooth cusp patterning. We demonstrate a correlation between Yap localization and cell proliferation in developing tooth germs. We also show that, between the cap stage and bell stage, Yap is crucial for the suppression of the primary enamel knot and for the patterning of secondary enamel knots, which are the future cusp regions. When Yap expression is stage-specifically knocked down during the cap stage, the activity of the primary enamel knot persists into the bell-stage tooth germ, leading to ectopic cusp formation. Our data reveal the importance of the Hippo pathway/Yap in enamel knots and in the proper patterning of tooth cusps.
Bibliographical noteFunding Information:
This research was supported by a grant of the Korea Health Technology R&D Project through the Korea Health Industry Development Institute (KHIDI), funded by the Ministry of Health & Welfare, Republic of Korea (HI14C3266). This research was supported by a grant of the Korea Health Technology R&D Project through the Korea Health Industry Development Institute (KHIDI), funded by the Ministry of Health & Welfare, Republic of Korea (HI14C1817). This work was supported by the National Research Foundation of Korea(NRF) grant funded by the Korea government(MSIP) (No. 2014R1A2A1A11050764).This research was supported by the Bio & Medical Technology Development Program of the National Research Foundation (NRF) funded by the Korean government (MSIP) (No. 2012M3A9B4028738).
© 2015, Springer-Verlag Berlin Heidelberg.
All Science Journal Classification (ASJC) codes
- Pathology and Forensic Medicine
- Cell Biology