Background
Lithium chloride (LiCl) is widely used for the treatment of manic and other psychotic disorders, but the administration of lithium can result in several congenital defects in the fetus, including cleft palate (Meng, Wang, Torensma, Jw & Bian, 2015) (Szabo, 1970). However, the mechanism of Lithium's action as a developmental toxicant in palatogenesis is not well known.
Conclusions
We concluded the LiCl-induced β-catenin overexpression delayed murine palatal shelf elevation by disturbing Cdc42 mediated F-actin cytoskeleton synthesis in the palatal mesenchyme.
Methods
In this study, hematoxylin-eosin and immunofluorescence staining were employed to evaluate the phenotypes and the expression of related markers in the LiCl-treated mice model. The palatal mesenchymal cells were cultured in vitro, and stimulated with LiCl or SKL2000, and co-treated with CASIN. β-catenin protein and other cytoskeleton associated markers were evaluated by Western blotting.
Results
We found that Lithium disrupted palate elevation by increasing the expression of β-catenin in C57BL/6J mice with the high incidence of cleft palate (62.5%). LiCl disturbed the F-actin responsible for cytoskeletal remodeling in mesenchymal cells, which proved to be essential in generating the elevating force during palatal elevation. Additionally, our Western blotting analysis revealed that the overexpression of β-catenin resulted in up-regulation of Cdc42, which mediated the downstream F-actin synthesis. Conclusions: We concluded the LiCl-induced β-catenin overexpression delayed murine palatal shelf elevation by disturbing Cdc42 mediated F-actin cytoskeleton synthesis in the palatal mesenchyme.