title: MiR-200b is involved in Tgf-β signaling to regulate mammalian palate development.
abstract: 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.
authors.affiliation: Division in Anatomy and Developmental Biology, Department of Oral Biology, Research Center for Orofacial Hard Tissue Regeneration, Brain Korea 21 Project, Oral Science Research Center, College of Dentistry, Yonsei University, 50 Yonsei-ro, Seodaemoon-Gu, Seoul 120-752, Korea.
authors.forename: Jeong-Oh
authors.initials: JO
authors.lastname: Shin
authors.forename: Jong-Min
authors.initials: JM
authors.lastname: Lee
authors.forename: Kyoung-Won
authors.initials: KW
authors.lastname: Cho
authors.forename: Sungwook
authors.initials: S
authors.lastname: Kwak
authors.forename: Hyuk-Jae
authors.initials: HJ
authors.lastname: Kwon
authors.forename: Min-Jung
authors.initials: MJ
authors.lastname: Lee
authors.forename: Sung-Won
authors.initials: SW
authors.lastname: Cho
authors.forename: Kye-Seong
authors.initials: KS
authors.lastname: Kim
authors.forename: Han-Sung
authors.initials: HS
authors.lastname: Jung
mesh_terms: D000818:Animals; D017209:Apoptosis; D015820:Cadherins / Q000235:genetics / Q000378:metabolism; D049109:Cell Proliferation; D057809:HEK293 Cells; D006801:Humans; D007150:Immunohistochemistry; D051379:Mice; D008813:Mice, Inbred ICR; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism*; D010159:Palate / Q000166:cytology / Q000254:growth & development* / Q000378:metabolism*; D060888:Real-Time Polymerase Chain Reaction; D015398:Signal Transduction / Q000235:genetics; D051899:Smad2 Protein / Q000235:genetics / Q000378:metabolism; D000071250:Snail Family Transcription Factors; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism; D016212:Transforming Growth Factor beta / Q000235:genetics / Q000378:metabolism*
chemical_list: D015820:Cadherins; D035683:MicroRNAs; C543719:Mirn200 microRNA, mouse; D051899:Smad2 Protein; C497783:Smad2 protein, mouse; D000071250:Snail Family Transcription Factors; D014157:Transcription Factors; D016212:Transforming Growth Factor beta
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