Small-molecule Wnt agonists correct cleft palates in Pax9 mutant mice in utero.

ABSTRACT: Clefts of the palate and/or lip are among the most common human craniofacial malformations and involve multiple genetic and environmental factors. Defects can only be corrected surgically and require complex life-long treatments. Our studies utilized the well-characterized Pax9^-/- mouse model with a consistent cleft palate phenotype to test small-molecule Wnt agonist therapies. We show that the absence of Pax9 alters the expression of Wnt pathway genes including Dkk1 and Dkk2, proven antagonists of Wnt signaling. The functional interactions between Pax9 and Dkk1 are shown by the genetic rescue of secondary palate clefts in Pax9^-/-Dkk1^f/+;Wnt1Cre embryos. The controlled intravenous delivery of small-molecule Wnt agonists (Dkk inhi

SUBMITTER: Jia S 

PROVIDER: S-EPMC5675451 | biostudies-literature | 2017 Oct

REPOSITORIES: biostudies-literature