Plastic Surgery Research Council
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ROLE OF EPITHELIUM-MESENCHYME INTERACTIONS DURING SOFT PALATE DEVELOPMENT
Presenter: Junichi Iwata, DDS, PhD
Co-Authors: Suzuki A; Sanchez-Lara PA; Urata M; Chai Y
University of Southern California

Cleft in the soft palate is one of the common cleft palates in humans, but it remains not well studied because few animal models exhibit isolated cleft in the soft palate. To elucidate the molecular mechanisms of cleft soft palate, we have used TGF≤br2fl/fl;K14-Cre mice as an established animal model for cleft soft palate. Based on imaging analyses using both three-dimensional microCT and histological reconstruction images, we have found that TGF≤br2fl/fl;K14-Cre mice exhibit decreased muscle mass, following defects in cell proliferation, differentiation, and maturation of myotubes into myofibers. Dickkopf (Dkk)1 and Dkk4, negative regulators of WNT/?-catenin signaling, are up-regulated in TGF≤br2 mutant cells and WNT/ ?-catenin signaling is disrupted in palatal mesenchymal cells of TGF≤br2fl/fl;K14-Cre mice. Moreover, neutralizing antibodies for DKK1 and DKK4 can rescue the muscle defect in the soft palate of TGF≤br2fl/fl;K14-Cre mice. Thus, our findings indicate that loss of TGF≤? signaling in epithelial cells compromises activation of WNT signaling and proper muscle development in the soft palate via tissue tissue interaction and results in cleft soft palate. Supported by NIDCR. R37 DE012711, U01 DE020065.


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