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Shh Plays an Inhibitory Role in Cusp Patterning by Regulation of Sostdc1

 J. Kim  ;  Y. Ahn  ;  D. Adasooriya  ;  E.J. Woo  ;  H.J. Kim  ;  K.S. Hu  ;  R. Krumlauf  ;  S.W. Cho 
 JOURNAL OF DENTAL RESEARCH, Vol.98(1) : 98-106, 2019 
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Shh protein ; Sostdc1 protein ; Wnt signaling pathway ; body patterning ; embryonic development ; tooth germ
Crown shapes in mammalian teeth vary considerably from species to species, and morphological characters in crown shape have been used to identify species. Cusp pattern is one of the characters in crown shape. In the processes governing the formation of cusp pattern, the Shh pathway has been implicated as an important player. Suppression of Shh signaling activity in vitro in explant assays appears to induce supernumerary cusp formation in wild-type tooth germs. However, the in vivo role of Shh signaling in cusp pattern formation and the molecular mechanisms by which Shh regulates cusp patterning are not clear. Here, through in vivo phenotypic analyses of mice in which Shh activity was suppressed and compared with wild-type mice, we characterized differences in the location, number, incidence, and shape of supernumerary cusps in molars at embryonic day 15.5. We found that the distances between cusps were reduced in molars of Shh activity-suppressed mice in vivo. These findings confirm and extend the previous idea that Shh acts as an inhibitor in the reaction-diffusion model for cusp pattern formation by negatively regulating the intercuspal distance. We uncovered a significant reduction of expression level of Sostdc1, which encodes a secreted modulator of Wnt signaling, after suppression of Shh activity. The supernumerary cusp formation in Sostdc1-/- mice and compound Sostdc1 and Lrp mutant mice indicates a strong association between Wnt and Shh signaling pathways in cusp patterning. In further support of this idea, there is a high degree of similarity in the supernumerary cusp patterns of mice lacking Sostdc1 or Shh at embryonic day 15.5. These results suggest that Shh plays an inhibitory role in cusp pattern formation by modulating Wnt signaling through the positive regulation of Sostdc1.
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2. College of Dentistry (치과대학) > Dept. of Oral Biology (구강생물학교실) > 1. Journal Papers
Yonsei Authors
Kim, Jin Sun(김진선) ORCID logo https://orcid.org/0000-0002-5089-3711
Kim, Hee Jin(김희진) ORCID logo https://orcid.org/0000-0002-1139-6261
Cho, Sung Won(조성원) ORCID logo https://orcid.org/0000-0001-7505-9769
Hu, Kyung Seok(허경석) ORCID logo https://orcid.org/0000-0002-9048-3805
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