Transcriptional regulation and functional characterization of FoxJ1 during oro-facial and pituitary morphogenesis.

摘要

FoxJ1 is identified as a new factor expressed during tooth and pituitary development. During morphogenesis of these organs FoxJ1 is co-expressed with Pitx2, Lef-1, and beta-catenin. Pitx2 binds to and activates the FoxJ1 promoter. Also Pitx2, Lef-1, and beta-catenin synergistically activate the FoxJ1 promoter. FoxJ1 interacts with Pitx2 and synergistically regulates its own activity. Further more FoxJ1 in concert with Pitx2, Lef-1, and beta-catenin dramatically increase its own activity providing a mechanism for early regulation of FoxJ1 during tooth and pituitary morphogenesis. FoxJ1-/- mice show a defective and poorly polarized ameloblasts with reduced amelogenin expression in the incisors and molars. Dlx-2 that has been shown to regulate amelogenin also regulates FoxJ1. Interestingly FoxJ1 interacts with Dlx-2 and synergistically regulates the Dlx-2 and FoxJ1 promoter providing a mechanism for FoxJ1 transcriptional regulation during late stages of tooth development. FoxJ1-/- mice also exhibit retarded growth, hypoplastic pituitary and reduced growth hormone (GH) expression. FoxJ1 and Pitx2 form a complex on GH promoter and synergistically activate the GH promoter. FoxJ1 in concert with Pitx2, Lef-1, and beta-catenin dramatically increase the GH activity accounting for retarded growth in FoxJ1-/- mice. Our data reveals a novel expression and transcriptional regulation of FoxJ1 during tooth and pituitary development.