title: Interactions between Shh, Sostdc1 and Wnt signaling and a new feedback loop for spatial patterning of the teeth.
abstract: Each vertebrate species displays specific tooth patterns in each quadrant of the jaw: the mouse has one incisor and three molars, which develop at precise locations and at different times. The reason why multiple teeth form in the jaw of vertebrates and the way in which they develop separately from each other have been extensively studied, but the genetic mechanism governing the spatial patterning of teeth still remains to be elucidated. Sonic hedgehog (Shh) is one of the key signaling molecules involved in the spatial patterning of teeth and other ectodermal organs such as hair, vibrissae and feathers. Sostdc1, a secreted inhibitor of the Wnt and Bmp pathways, also regulates the spatial patterning of teeth and hair. Here, by utilizing maternal transfer of 5E1 (an anti-Shh antibody) to mouse embryos through the placenta, we show that Sostdc1 is downstream of Shh signaling and suggest a Wnt-Shh-Sostdc1 negative feedback loop as a pivotal mechanism controlling the spatial patterning of teeth. Furthermore, we propose a new reaction-diffusion model in which Wnt, Shh and Sostdc1 act as the activator, mediator and inhibitor, respectively, and confirm that such interactions can generate the tooth pattern of a wild-type mouse and can explain the various tooth patterns produced experimentally.
authors: Division in Anatomy and Developmental Biology, Department of Oral Biology, Research Center for Orofacial Hard Tissue Regeneration, Brain Korea 21 Project, Oral Science Research Center, Yonsei University College of Dentistry, Seoul 120-752, Korea.
authors: Sung-Won
authors: SW
authors: Cho
authors: Sungwook
authors: S
authors: Kwak
authors: Thomas E
authors: TE
authors: Woolley
authors: Min-Jung
authors: MJ
authors: Lee
authors: Eun-Jung
authors: EJ
authors: Kim
authors: Ruth E
authors: RE
authors: Baker
authors: Hee-Jin
authors: HJ
authors: Kim
authors: Jeon-Soo
authors: JS
authors: Shin
authors: Cheryll
authors: C
authors: Tickle
authors: Philip K
authors: PK
authors: Maini
authors: Han-Sung
authors: HS
authors: Jung
mesh_terms: D048868:Adaptor Proteins, Signal Transducing; D000818:Animals; D019521:Body Patterning / Q000235:genetics* / Q000502:physiology; D019485:Bone Morphogenetic Proteins / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D002478:Cells, Cultured; D003198:Computer Simulation; D004622:Embryo, Mammalian; D004843:Epistasis, Genetic / Q000502:physiology; D025461:Feedback, Physiological / Q000502:physiology*; D053823:Hedgehog Proteins / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D051379:Mice; D018345:Mice, Knockout; D008819:Mice, Nude; D008962:Models, Theoretical; D009805:Odontogenesis / Q000235:genetics / Q000502:physiology; D015398:Signal Transduction / Q000235:genetics / Q000502:physiology; D014070:Tooth / Q000196:embryology* / Q000378:metabolism; D051153:Wnt Proteins / Q000235:genetics / Q000378:metabolism / Q000502:physiology*
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D019485:Bone Morphogenetic Proteins; D053823:Hedgehog Proteins; C465570:Shh protein, mouse; C483887:Sostdc1 protein, mouse; D051153:Wnt Proteins