Forkhead box F2 Regulation of Platelet-Derived Growth Factor and myocardin/Serum Response Factor Signaling is Essential for Intestinal Development

摘要: Alterations in the forkhead box F2 gene expression have been reported numerous pathologies, and Foxf2−/− mice are perinatal lethal with multiple malformations; however, molecular mechanisms pertaining to Foxf2 signaling severely lacking. In this study, requirements murine smooth muscle cells were examined using a conditional knock-out approach. We generated novel Foxf2-floxed mice, which we bred smMHC-Cre-eGFP generate mouse line deleted specifically from muscle. These exhibited growth retardation due reduced intestinal length as well inflammation remodeling of small intestine. Colons Tg(smMHC-Cre-eGFP+/−);Foxf2−/− had expansion myenteric nerve plexus increased proliferation leading thickening longitudinal layer. deficiency colonic was associated Foxf1, PDGFa, PDGFb, PDGF receptor α, myocardin. FOXF2 bound promoter regions these genes indicating direct transcriptional regulation. repressed Foxf1 activity co-transfection experiments. also show that knockdown vitro transgenic myocardin/serum response factor contractile proteins. attenuated through binding N-terminal region Our results indicate is essential for development serum signaling.