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

J. Kim, Y. Ahn, D. Adasooriya, E. J. Woo, H. J. Kim, Kyung-Seok Hu, R. Krumlauf, S. W. Cho

Research output: Contribution to journalArticle

1 Citation (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)98-106
Number of pages9
JournalJournal of Dental Research
Volume98
Issue number1
DOIs
Publication statusPublished - 2019 Jan 1

Fingerprint

Crowns
Tooth Germ
Wnt Signaling Pathway
Tooth
Incidence

All Science Journal Classification (ASJC) codes

  • Dentistry(all)

Cite this

Kim, J., Ahn, Y., Adasooriya, D., Woo, E. J., Kim, H. J., Hu, K-S., ... Cho, S. W. (2019). Shh Plays an Inhibitory Role in Cusp Patterning by Regulation of Sostdc1. Journal of Dental Research, 98(1), 98-106. https://doi.org/10.1177/0022034518803095
Kim, J. ; Ahn, Y. ; Adasooriya, D. ; Woo, E. J. ; Kim, H. J. ; Hu, Kyung-Seok ; Krumlauf, R. ; Cho, S. W. / Shh Plays an Inhibitory Role in Cusp Patterning by Regulation of Sostdc1. In: Journal of Dental Research. 2019 ; Vol. 98, No. 1. pp. 98-106.
@article{c15f50462b6a427784fe76222e801cf7,
title = "Shh Plays an Inhibitory Role in Cusp Patterning by Regulation of Sostdc1",
abstract = "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.",
author = "J. Kim and Y. Ahn and D. Adasooriya and Woo, {E. J.} and Kim, {H. J.} and Kyung-Seok Hu and R. Krumlauf and Cho, {S. W.}",
year = "2019",
month = "1",
day = "1",
doi = "10.1177/0022034518803095",
language = "English",
volume = "98",
pages = "98--106",
journal = "Journal of Dental Research",
issn = "0022-0345",
publisher = "SAGE Publications Inc.",
number = "1",

}

Kim, J, Ahn, Y, Adasooriya, D, Woo, EJ, Kim, HJ, Hu, K-S, Krumlauf, R & Cho, SW 2019, 'Shh Plays an Inhibitory Role in Cusp Patterning by Regulation of Sostdc1', Journal of Dental Research, vol. 98, no. 1, pp. 98-106. https://doi.org/10.1177/0022034518803095

Shh Plays an Inhibitory Role in Cusp Patterning by Regulation of Sostdc1. / Kim, J.; Ahn, Y.; Adasooriya, D.; Woo, E. J.; Kim, H. J.; Hu, Kyung-Seok; Krumlauf, R.; Cho, S. W.

In: Journal of Dental Research, Vol. 98, No. 1, 01.01.2019, p. 98-106.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Shh Plays an Inhibitory Role in Cusp Patterning by Regulation of Sostdc1

AU - Kim, J.

AU - Ahn, Y.

AU - Adasooriya, D.

AU - Woo, E. J.

AU - Kim, H. J.

AU - Hu, Kyung-Seok

AU - Krumlauf, R.

AU - Cho, S. W.

PY - 2019/1/1

Y1 - 2019/1/1

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=85058987365&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85058987365&partnerID=8YFLogxK

U2 - 10.1177/0022034518803095

DO - 10.1177/0022034518803095

M3 - Article

VL - 98

SP - 98

EP - 106

JO - Journal of Dental Research

JF - Journal of Dental Research

SN - 0022-0345

IS - 1

ER -