title: Mesenchymal signaling in dorsoventral differentiation of palatal epithelium.
abstract: After palatal fusion, the dorsal and ventral epithelia of the palatal shelf differentiate into the nasal and oral mucosa, respectively. The tissue-specific differentiation of palatal epithelia along the dorsal-ventral axis is regulated by the signaling molecules expressed in the underlying mesenchyme. Thus, as in many other epithelial organs, differentiation relies on epithelial-mesenchymal interactions. To screen for region-specific mesenchymal signaling molecules that determine the fate of the palatal epithelia, we employed a laser microdissection (LMD) method. LMD allowed us to collect region-specific mesenchymal tissues at E13, prior to palatal fusion and the development of distinct dorsal and ventral epithelial morphology. Genome-wide screening was performed on the tissues collected using LMD to identify candidate mesenchymal signaling molecules. The microarray results were validated using real-time quantitative (qPCR) and in situ hybridization methods. The developmental role and interactions of the candidate genes were evaluated in in vitro-cultivated E13 palates using an anti-sense oligodeoxynucleotide (AS-ODN)-based loss-of-function approach. Apparent changes in the expression patterns of Runt-related transcription factor 2 (Runx2) and LIM homeobox 8 (Lhx8) were observed after knocking down each gene. Knock-down of Runx2 and Lhx8 also altered the immunolocalization pattern of cytokeratin18 (CK18), an established marker for nasal epithelium. These results were confirmed using Runx2 heterozygote mice. The mesenchymal signaling molecules Runx2 and Lhx8, which possess region-specific expression patterns along the dorsoventral axis, functionally interact to regulate the cellular and molecular characteristics of dorsal and ventral epithelia, suggesting that mesenchymal signaling molecules determine the dorsoventral fate of epithelial structures in the developing palate.
authors.affiliation: Department of Biochemistry, School of Dentistry, IHBR, Kyungpook National University, 2177 Dalgubeol-daero, Joong-gu,, Daegu, 700-412, South Korea.
authors.forename: Wern-Joo
authors.initials: WJ
authors.lastname: Sohn
authors.affiliation: Department of Biochemistry, School of Dentistry, IHBR, Kyungpook National University, 2177 Dalgubeol-daero, Joong-gu,, Daegu, 700-412, South Korea.
authors.forename: Gi-Jeong
authors.initials: GJ
authors.lastname: Gwon
authors.affiliation: School of Life Science and Biotechnology, Kyungpook National University, Daegu, South Korea.
authors.forename: Hyeng-Soo
authors.initials: HS
authors.lastname: Kim
authors.affiliation: Department of Biochemistry, School of Dentistry, IHBR, Kyungpook National University, 2177 Dalgubeol-daero, Joong-gu,, Daegu, 700-412, South Korea.
authors.forename: Sanjiv
authors.initials: S
authors.lastname: Neupane
authors.affiliation: Department of Biology, College of Natural Sciences, Chungbuk National University, Cheongju, Chungbuk, South Korea.
authors.forename: Sung-Jin
authors.initials: SJ
authors.lastname: Cho
authors.affiliation: Department of Maxillofacial Biomedical Engineering, School of Dentistry, Kyung Hee University, Seoul, South Korea.
authors.forename: Jae-Hyung
authors.initials: JH
authors.lastname: Lee
authors.affiliation: Department of Histology and Developmental Biology, Tokyo Dental College, Tokyo, Japan.
authors.forename: Hitoshi
authors.initials: H
authors.lastname: Yamamoto
authors.affiliation: Department of Biochemistry and Cell Biology, School of Medicine, Cell and Matrix Research Institute, Skeletal Diseases Genome Research Center, Kyungpook National University, Daegu, South Korea.
authors.forename: Je-Yong
authors.initials: JY
authors.lastname: Choi
authors.affiliation: Department of Oral and Maxillofacial Radiology, School of Dentistry, IHBR, Kyungpook National University, Daegu, South Korea.
authors.forename: Chang-Hyeon
authors.initials: CH
authors.lastname: An
authors.affiliation: Department of Biochemistry, School of Dentistry, IHBR, Kyungpook National University, 2177 Dalgubeol-daero, Joong-gu,, Daegu, 700-412, South Korea.
authors.forename: Youngkyun
authors.initials: Y
authors.lastname: Lee
authors.affiliation: Department of Oral Pathology and Regenerative Medicine, School of Dentistry, IHBR, Kyungpook National University, Daegu, South Korea.
authors.forename: Hong-In
authors.initials: HI
authors.lastname: Shin
authors.affiliation: School of Life Science and Biotechnology, Kyungpook National University, Daegu, South Korea.
authors.forename: Sanggyu
authors.initials: S
authors.lastname: Lee
authors.affiliation: Department of Biochemistry, School of Dentistry, IHBR, Kyungpook National University, 2177 Dalgubeol-daero, Joong-gu,, Daegu, 700-412, South Korea. jykim91@knu.ac.kr.
authors.forename: Jae-Young
authors.initials: JY
authors.lastname: Kim
mesh_terms: D000818:Animals; D019521:Body Patterning; D002454:Cell Differentiation; D004848:Epithelium / Q000196:embryology*; D020869:Gene Expression Profiling; D018507:Gene Expression Regulation, Developmental; D056726:Genetic Association Studies; D016678:Genome; D017403:In Situ Hybridization; D053538:Keratin-18 / Q000378:metabolism; D061346:Laser Capture Microdissection; D008648:Mesoderm / Q000166:cytology / Q000378:metabolism*; D008813:Mice, Inbred ICR; D020411:Oligonucleotide Array Sequence Analysis; D009924:Organ Culture Techniques; D009928:Organ Specificity; D038081:Organogenesis; D010159:Palate / Q000166:cytology / Q000196:embryology*; D060888:Real-Time Polymerase Chain Reaction; D015203:Reproducibility of Results; D015398:Signal Transduction
chemical_list: D053538:Keratin-18
keywords: Dorsal and ventral patterning; Epithelial differentiation; Epithelial–mesenchymal interactions; Genome–wide screening; Palatal development