4.3 Article

Inhibition of smoothened receptor by vismodegib leads to micrognathia during embryogenesis

Journal

DIFFERENTIATION
Volume 125, Issue -, Pages 27-34

Publisher

ELSEVIER SCI LTD
DOI: 10.1016/j.diff.2022.04.001

Keywords

Mandible; Meckel?s cartilage; Smoothened; Sonic hedgehog; Proliferation

Funding

  1. Natural Science Foundation of Fujian Province, China [2019J02011]
  2. Natural Science Foundation of Fujian Province of China [2018J01823]
  3. Open subject project of Fujian Provincial Oral Biomaterial Engineering Technology Research Center/Fujian Provincial Key Laboratory of Stomatology [2019kq07]

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The mandible is an important part of the craniofacial skeleton and its development involves multiple signaling pathways. The function of the hedgehog signaling pathway is crucial for mandibular development.
The mandible is an important part of the craniofacial skeleton. Mandibular development is complex and involves multiple signaling pathways. These signaling pathways participate in a complex regulatory mechanism to regulate mandibular growth. The function of hedgehog signaling has previously been shown to be crucial for mandibular arch development. We treated pregnant ICR mice with the hedgehog pathway inhibitor vismodegib by oral gavage to establish a micrognathia model, which was mandible development defective. Compared to control, this model exhibited reduced mesenchymal cell proliferation and increased apoptosis. The development of the Meckel's cartilage and the condensations of mesenchymal cells were delayed by approximately one day in treated embryos. These results reveal that Smoothened may have shaped the mandible during mandibular growth by ensuring cell survival, proliferation, and development of Merkel's cartilage.

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