Inhibition of smoothened receptor by vismodegib leads to micrognathia during embryogenesis.

Abstract

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.

• Authors: Yan Guo, Di Wu, QingJiang Xu, Weihui Chen
• Journal: Differentiation; research in biological diversity (Differentiation) 2022 May-Jun Vol. 125 Pg. 27-34 ISSN: 1432-0436 [Electronic] England
• PMID: 35429807 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2022 International Society of Differentiation. Published by Elsevier B.V. All rights reserved.

Chemical References

• Anilides
• Hedgehog Proteins
• HhAntag691
• Pyridines
• Smoothened Receptor

Topics

• Anilides
• Animals
• Embryonic Development (genetics)
• Hedgehog Proteins (genetics, metabolism)
• Mandible
• Mice
• Mice, Inbred ICR
• Micrognathism (metabolism)
• Pyridines
• Smoothened Receptor (genetics, metabolism)