ArticleInternational dental journal2026
Effects of Smoothened Agonist Exposure on Murine Craniofacial Development.
Article in International dental journal, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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8 authors.
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Abstract
objectiveWhile inhibition of Hedgehog (Hh) signalling is known to cause cleft lip, the effects of its hyperactivation on craniofacial development remain systematically unexplored. MATERIALS AND
methodsPregnant 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).
resultsSAG 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.
conclusionSAG 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.
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