role of gsk-3β in the osteogenic differentiation of palatal mesenchyme成骨分化的作用gsk-3β腭间质.pdfVIP

Role of GSK-3b in the Osteogenic Differentiation of Palatal Mesenchyme 1. 1. 1 1 2 1,3 Emily R. Nelson , Benjamin Levi , Michael Sorkin , Aaron W. James , Karen J. Liu , Natalina Quarto , Michael T. Longaker1,4* 1 Hagey Laboratory for Pediatric Regenerative Medicine, Plastic and Reconstructive Surgery Division, Department of Surgery, Stanford University School of Medicine, Stanford, California, United States of America, 2 Department of Craniofacial Development, King’s College London, London, United Kingdom, 3 Dipartimento di Scienze Chirurgiche, Anestesiologiche-Rianimatorie e dell ‘Emergenza ‘‘Giuseppe Zannini,’’ Universita’ degli Studi di Napoli Federico II, Napoli, Italy, 4 Institute for Stem Cell Biology and Regenerative Medicine, Stanford University, Stanford, California, United States of America Abstract Introduction: The function of Glycogen Synthase Kinases 3b (GSK-3b) has previously been shown to be necessary for normal secondary palate development. Using GSK-3ß null mouse embryos, we examine the potential coordinate roles of Wnt and Hedgehog signaling on palatal ossification. Methods: Palates were harvested from GSK-3b, embryonic days 15.0–18.5 (e15.0–e18.5), and e15.5 Indian Hedgehog (Ihh) null embryos, and their wild-type littermates. The phenotype of GSK-3b null embryos was analyzed with skeletal whole mount and pentachrome stains. Spatiotemporal regulation of osteogenic gene expression, in addition to Wnt and Hedgehog signaling activity, were examined in vivo on GSK-3b and Ihh +/+ and 2/ 2 e15.5 embryos using in situ hybridization and immunohistochemistry. To corroborate these results, expression of the same molecular targets we