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Updated: Jun 13, 2026
Analysis of Craniomaxillofacial Malformations in Mice Using Three-dimensional Microcomputed Tomography
Published on: January 17, 2025
Effects of Smoothened Agonist Exposure on Murine Craniofacial Development
Chuanqing Mao1, Yuanjing Jiang2, Zuhui Li1
1Department of Oral and Maxillofacial Surgery, Fujian Medical University Union Hospital, Fuzhou, China; Clinical Research Center for Oral Tissue Deficiency Diseases of Fujian Province & Fujian Key Laboratory of Oral Diseases & Fujian Provincial Engineering Research Center of Oral Biomaterial, School and Hospital of Stomatology, Fujian Medical University, Fuzhou, China.
Objective:
While inhibition of Hedgehog (Hh) signalling is known to cause cleft lip, the effects of its hyperactivation on craniofacial development remain systematically unexplored.
Materials And Methods:
Pregnant mice received a single intraperitoneal injection of Smoothened Agonist (SAG) (25 mg/kg) at various time points between E7.5 and E12.5. A median cleft lip model was established at E10.5. Mechanisms were assessed by analysing cell proliferation (PHH3, Ki67), apoptosis (TUNEL), and expression of cell cycle regulators (Cyclin A, B1, D1, E1).
Results:
SAG administration induced craniofacial defects - including cranial bone abnormalities, hematomas, and cleft lip/palate - in a time-dependent manner. The critical window for cleft lip induction was E9.5-E10.5. Mechanistically, SAG-induced cleft lip was associated with reduced proliferation and altered expression of selected cell-cycle markers, consistent with delayed G0/G1 progression. No significant change in apoptosis was observed.
Conclusion:
SAG is a potent teratogen that can induce cleft lip during a critical developmental window, potentially through suppression of cell proliferation and perturbation of cell-cycle progression. While its prenatal use poses significant risks, SAG also provides a useful experimental tool for generating congenital craniofacial defect models.
