title: Hippo pathway/Yap regulates primary enamel knot and dental cusp patterning in tooth morphogenesis.
abstract: 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.
authors: Division in Anatomy and Developmental Biology, Department of Oral Biology, BK21 PLUS project, Oral Science Research Institute, College of Dentistry, Yonsei Center of Biotechnology, Yonsei University, 50 Yonsei-Ro, Seodaemun-Gu, Seoul, 120-752, Republic of Korea.|Division of Developmental Biology, Cincinnati Children's Hospital Medical Center, Cincinnati, OH 45229, USA.
authors: Hyuk-Jae Edward
authors: HJ
authors: Kwon
authors: Division in Anatomy and Developmental Biology, Department of Oral Biology, BK21 PLUS project, Oral Science Research Institute, College of Dentistry, Yonsei Center of Biotechnology, Yonsei University, 50 Yonsei-Ro, Seodaemun-Gu, Seoul, 120-752, Republic of Korea.
authors: Liwen
authors: L
authors: Li
authors: Division in Anatomy and Developmental Biology, Department of Oral Biology, BK21 PLUS project, Oral Science Research Institute, College of Dentistry, Yonsei Center of Biotechnology, Yonsei University, 50 Yonsei-Ro, Seodaemun-Gu, Seoul, 120-752, Republic of Korea. hsj8076@gmail.com.|Oral Biosciences, Faculty of Dentistry, The University of Hong Kong, Hong Kong, SAR, People's Republic of China. hsj8076@gmail.com.
authors: Han-Sung
authors: HS
authors: Jung
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D018797:Cell Cycle Proteins; D003743:Dental Enamel / Q000378:metabolism*; D004848:Epithelium / Q000378:metabolism; D018507:Gene Expression Regulation, Developmental / Q000502:physiology; D000090683:Hippo Signaling Pathway; D008297:Male; D051379:Mice; D009024:Morphogenesis / Q000235:genetics / Q000502:physiology*; D009805:Odontogenesis / Q000235:genetics / Q000502:physiology*; D010750:Phosphoproteins / Q000235:genetics / Q000378:metabolism*; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism; D015398:Signal Transduction; D014070:Tooth / Q000254:growth & development*; D014083:Tooth Germ / Q000378:metabolism*; D000091102:YAP-Signaling Proteins
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D018797:Cell Cycle Proteins; D010750:Phosphoproteins; D000091102:YAP-Signaling Proteins; C486223:Yap1 protein, mouse; D017346:Protein Serine-Threonine Kinases
keywords: Cell proliferation; Enamel knot; Hippo pathway; Tooth cusp patterning; Yap