title: Modulation of cell proliferation during palatogenesis by the interplay between Tbx3 and Bmp4.
abstract: During secondary palate development, two shelves are elevated to a horizontal position above the tongue through a process involving many cellular mechanisms, including proliferation. In particular, the expression patterns of Tbx3 and Bmp4, which are colocalized at embryonic day 13.5 (E13.5) and have unique expression patterns in specific regions at E14.5, have been investigated in early mouse palatogenesis. Tbx3 expression is reported to be associated with Bmp4 signaling during the process of organogenesis in other areas, such as limb development. However, the function of Tbx3 and the relationship between Tbx3 and Bmp4 in palate development have not been determined. We have examined the gene expression pattern and cell proliferation in order to understand the mutual interactions and function of Tbx3 and Bmp4. An electroporation method was used to investigate the altered pattern of these genes after their over-expression in organ cultures. NOGGIN protein-soaked beads were also implanted into the cultured palate to determine the function of Bmp4 in palatogenesis. After electroporation and NOGGIN bead implantation, the number of PCNA-positive cells was counted. The results showed that Tbx3 and Bmp4 strongly up- and down-regulated each other in order to control the proliferation of the palatal shelf. Thus, Tbx3 expression is induced by Bmp4 in the mesenchyme of the anterior palatal shelves, whereas mesenchymal expression of Tbx3 down-regulates Bmp4 expression in the mesenchyme of the palate. The harmonization between Tbx3 and Bmp4 therefore controls cell proliferation to regulate secondary palate development.
authors.affiliation: Division in Anatomy and Developmental Biology, Department of Oral Biology, College of Dentistry, Yonsei University, 134 Shinchon-Dong, Seodaemoon-Gu, Seoul, South Korea.
authors.forename: Jong-Min
authors.initials: JM
authors.lastname: Lee
authors.forename: Jae-Young
authors.initials: JY
authors.lastname: Kim
authors.forename: Kyoung-Won
authors.initials: KW
authors.lastname: Cho
authors.forename: Min-Jung
authors.initials: MJ
authors.lastname: Lee
authors.forename: Sung-Won
authors.initials: SW
authors.lastname: Cho
authors.forename: Yanding
authors.initials: Y
authors.lastname: Zhang
authors.forename: Seong-Kyu
authors.initials: SK
authors.lastname: Byun
authors.forename: Choong-Kook
authors.initials: CK
authors.lastname: Yi
authors.forename: Han-Sung
authors.initials: HS
authors.lastname: Jung
mesh_terms: D000818:Animals; D055415:Bone Morphogenetic Protein 4; D019485:Bone Morphogenetic Proteins / Q000235:genetics*; D002352:Carrier Proteins / Q000494:pharmacology; D049109:Cell Proliferation; D004847:Epithelial Cells / Q000166:cytology; D018507:Gene Expression Regulation, Developmental / Q000187:drug effects; D017403:In Situ Hybridization; D008648:Mesoderm / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D051379:Mice; D008813:Mice, Inbred ICR; D009924:Organ Culture Techniques; D010159:Palate / Q000166:cytology / Q000196:embryology / Q000378:metabolism*; D018809:Proliferating Cell Nuclear Antigen / Q000378:metabolism; D020825:T-Box Domain Proteins / Q000235:genetics*; D014162:Transfection; D000099176:Noggin Protein
chemical_list: D055415:Bone Morphogenetic Protein 4; D019485:Bone Morphogenetic Proteins; D002352:Carrier Proteins; D018809:Proliferating Cell Nuclear Antigen; D020825:T-Box Domain Proteins; D000099176:Noggin Protein; C525810:Bmp4 protein, mouse; C491460:Tbx3 protein, mouse