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

Research output: Contribution to journalArticlepeer-review

75 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)1807-1816
Number of pages10
JournalDevelopment
Volume138
Issue number9
DOIs
Publication statusPublished - 2011 May

All Science Journal Classification (ASJC) codes

  • Molecular Biology
  • Developmental Biology

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