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Interactions between Shh, Sostdc1 and Wnt signaling and a new feedback loop for spatial patterning of the teeth

 Sung-Won Cho  ;  Sungwook Kwak  ;  Thomas E. Woolley  ;  Min-Jung Lee  ;  Eun-Jung Kim  ;  Ruth E. Baker  ;  Hee-Jin Kim  ;  Jeon-Soo Shin  ;  Cheryll Tickle  ;  Philip K. Maini  ;  Han-Sung Jung 
 DEVELOPMENT, Vol.138(9) : 1807-1816, 2011 
Journal Title
Issue Date
Animals ; Body Patterning/genetics* ; Body Patterning/physiology ; Bone Morphogenetic Proteins/genetics ; Bone Morphogenetic Proteins/metabolism ; Bone Morphogenetic Proteins/physiology* ; Cells, Cultured ; Computer Simulation ; Embryo, Mammalian ; Epistasis, Genetic/physiology ; Feedback, Physiological/physiology* ; Hedgehog Proteins/genetics ; Hedgehog Proteins/metabolism ; Hedgehog Proteins/physiology* ; Mice ; Mice, Knockout ; Mice, Nude ; Models, Theoretical ; Odontogenesis/genetics ; Odontogenesis/physiology ; Signal Transduction/genetics ; Signal Transduction/physiology ; Tooth/embryology* ; Tooth/metabolism ; Wnt Proteins/genetics ; Wnt Proteins/metabolism ; Wnt Proteins/physiology*
Shh ; Sostdc1 ; Wnt ; Feedback loop ; Tooth patterning ; Mouse
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.
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2. College of Dentistry (치과대학) > Dept. of Oral Biology (구강생물학교실) > 1. Journal Papers
1. College of Medicine (의과대학) > Dept. of Microbiology (미생물학교실) > 1. Journal Papers
5. Research Institutes (연구소) > Research Center for Orofacial Hard Tissue Regeneration (구강악안면경조직재생연구센터) > 1. Journal Papers
Yonsei Authors
Kwak, Sung Wook(곽성욱)
Kim, Eun-Jung(김은정) ORCID logo https://orcid.org/0000-0002-9515-7590
Kim, Hee Jin(김희진) ORCID logo https://orcid.org/0000-0002-1139-6261
Shin, Jeon Soo(신전수) ORCID logo https://orcid.org/0000-0002-8294-3234
Lee, Min Jung(이민정)
Jung, Han Sung(정한성) ORCID logo https://orcid.org/0000-0003-2795-531X
Cho, Sung Won(조성원) ORCID logo https://orcid.org/0000-0001-7505-9769
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