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Sohn W.-J.,Kyungpook National University | Ji Y.-R.,Kyungpook National University | Kim H.-S.,Kyungpook National University | Gwon G.-J.,Kyungpook National University | And 7 more authors.
Mechanisms of Development | Year: 2012

Palatal development is one of the critical events in craniofacial morphogenesis. During fusion of the palatal shelves, removal of the midline epithelial seam (MES) is a fundamental process for achieving proper morphogenesis of the palate. The reported mechanisms for removing the MES are the processes of apoptosis, migration or general epithelial-to-mesenchymal transition (EMT) through modulations of various signaling molecules including Wnt signaling. RGS19, a regulator of the G protein signaling (RGS) family, interacts selectively with the specific α subunits of the G proteins (Gαi, Gαq) and enhances their GTPase activity. Rgs19 was reported to be a modulator of the Wnt signaling pathway. In mouse palatogenesis, the restricted epithelial expression pattern of Rgs19 was examined in the palatal shelves, where expression of Wnt11 was observed. Based on these specific expression patterns of Rgs19 in the palatal shelves, the present study examined the detailed developmental function of Rgs19 using AS-ODN treatments during in vitro palate organ cultivations as a loss-of-function study. After the knockdown of Rgs19, the morphological changes in the palatal shelves was examined carefully using a computer-aided three dimensional reconstruction method and the altered expression patterns of related signaling molecules were evaluated using genome wide screening methods. RT-qPCR and in situ hybridization methods were also used to confirm these array results. These morphological and molecular examinations suggested that Rgs19 plays important roles in palatal fusion through the degradation of MES via activation of the palatal fusion related and apoptotic related genes. Overall, inhibition of the proliferation related and Wnt responsive genes by Rgs19 are required for proper palatal fusion. © 2012 Elsevier Ireland Ltd.


Shin J.-O.,Research Center for Orofacial Hard Tissue Regeneration | Kim E.-J.,Research Center for Orofacial Hard Tissue Regeneration | Cho K.-W.,Research Center for Orofacial Hard Tissue Regeneration | Nakagawa E.,Research Center for Orofacial Hard Tissue Regeneration | And 3 more authors.
Histochemistry and Cell Biology | Year: 2012

Tooth morphogenesis is regulated by sequential and reciprocal interaction between oral epithelium and neural-crest-derived ectomesenchyme. The interaction is controlled by various signal molecules such as bone morphogenetic protein (BMP), Hedgehog, Wbroblast growth factor (FGF), and Wnt. Zeb family is known as a transcription factor, which is essential for neural development and neural-crest-derived tissues, whereas the role of the Zeb family in tooth development remains unclear. Therefore, this study aimed to investigate the expression proWles of Zeb1 and Zeb2 during craniofacial development focusing on mesenchyme of palate, hair follicle, and tooth germ from E12.5 to E16.5. In addition, we examined the interaction between Zeb family and BMP4 during tooth development. Both Zeb1 and Zeb2 were expressed at mesenchyme of the palate, hair follicle, and tooth germ throughout the stages. In the case of tooth germ at the cap stage, the expression of Zeb1 and Zeb2 was lost in epithelium-separated dental mesenchyme. However, the expression of Zeb1 and Zeb2 in the dental mesenchyme was recovered by Bmp4 signaling via BMP4-soaked bead and tissue recombination. Our results suggest that Zeb1 and Zeb2, which were mediated by BMP4, play an important role in neural-crestderived craniofacial organ morphogenesis, such as tooth development. © Springer-Verlag 2012.


Shin J.-O.,Research Center for Orofacial Hard Tissue Regeneration | Lee J.-M.,Research Center for Orofacial Hard Tissue Regeneration | Cho K.-W.,Research Center for Orofacial Hard Tissue Regeneration | Kwak S.,Research Center for Orofacial Hard Tissue Regeneration | And 5 more authors.
Histochemistry and Cell Biology | Year: 2012

Various cellular and molecular events are involved in palatogenesis, including apoptosis, epithelial- mesenchymal transition (EMT), cell proliferation, and cell migration. Smad2 and Snail, which are well-known key mediators of the transforming growth factor beta (Tgf-β) pathway, play a crucial role in the regulation of palate development. Regulatory effects of microRNA 200b (miR- 200b) on Smad2 and Snail in palatogenesis have not yet been elucidated. The aim of this study is to determine the relationship between palate development regulators miR-200b and Tgf-β-mediated genes. Expression of miR-200b, E-cadherin, Smad2, and Snail was detected in the mesenchyme of the mouse palate, while miR-200b was expressed in the medial edge epithelium (MEE) and palatal mesenchyme. After the contact of palatal shelves, miR- 200b was no longer expressed in the mesenchyme around the fusion region. The binding activity of miR-200b to both Smad2 and Snail was examined using a luciferase assay. MiR-200b directly targeted Smad2 and Snail at both cellular and molecular levels. The function of miR-200b was determined by overexpression via a lentiviral vector in the palatal shelves. Ectopic expression of miR-200b resulted in suppression of these Tgf-β-mediated regulators and changes of apoptosis and cell proliferation in the palatal fusion region. These results suggest that miR-200b plays a crucial role in regulating the Smad2, Snail, and in apoptosis during palatogenesis by acting as a direct non-coding, influencing factor. Furthermore, the molecular interactions between miR-200b and Tgf-β signaling are important for proper palatogenesis and especially for palate fusion. Elucidating the mechanism of palatogenesis may aid the design of effective gene-based therapies for the treatment of congenital cleft palate. © Springer-Verlag 2011.

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