title: Fine tuning of Rac1 and RhoA alters cuspal shapes by remolding the cellular geometry.
abstract: The anatomic and functional combinations of cusps and lophs (ridges) define the tooth shape of rodent molars, which distinguishes species. The species-specific cusp patterns result from the spatiotemporal induction of enamel knots (EKs), which require precisely controlled cellular behavior to control the epithelial invagination. Despite the well-defined roles of EK in cusp patterning, the determinants of the ultimate cuspal shapes and involvement of epithelial cellular geometry are unknown. Using two typical tooth patterns, the lophodont in gerbils and the bunodont in mice, we showed that the cuspal shape is determined by the dental epithelium at the cap stage, whereas the cellular geometry in the inner dental epithelium (IDE) is correlated with the cuspal shape. Intriguingly, fine tuning Rac1 and RhoA interconvert cuspal shapes between two species by remolding the cellular geometry. Either inhibition of Rac1 or ectopic expression of RhoA could region-distinctively change the columnar shape of IDE cells in gerbils to drive invagination to produce cusps. Conversely, RhoA reduction in mice inhibited invagination and developed lophs. Furthermore, we found that Rac1 and RhoA modulate the choices of cuspal shape by coordinating adhesion junctions, actin distribution, and fibronectin localization to drive IDE invagination.
authors.affiliation: Division in Anatomy and Developmental Biology, Department of Oral Biology, Oral Science Research Center, BK21 PLUS Project, Yonsei University College of Dentistry, Seoul, Korea.
authors.forename: Liwen
authors.initials: L
authors.lastname: Li
authors.affiliation: Division in Anatomy and Developmental Biology, Department of Oral Biology, Oral Science Research Center, BK21 PLUS Project, Yonsei University College of Dentistry, Seoul, Korea.
authors.forename: Qinghuang
authors.initials: Q
authors.lastname: Tang
authors.affiliation: Department of Oral Biology, Tohoku University Graduate School of Dentistry, Sendai, Japan.
authors.forename: Takashi
authors.initials: T
authors.lastname: Nakamura
authors.affiliation: Department of Medical Genetics, Hallym University College of Medicine, Chuncheon, Korea.
authors.forename: Jun-Gyo
authors.initials: JG
authors.lastname: Suh
authors.affiliation: Division of Anatomy and Cell Biology of the Hard Tissue, Department of Tissue Regeneration and Reconstruction, Niigata University Graduate School of Medical and Dental Sciences, Niigata, Japan.
authors.forename: Hayato
authors.initials: H
authors.lastname: Ohshima
authors.affiliation: Division in Anatomy and Developmental Biology, Department of Oral Biology, Oral Science Research Center, BK21 PLUS Project, Yonsei University College of Dentistry, Seoul, Korea.|Oral Biosciences, Faculty of Dentistry, The University of Hong Kong, Hong Kong SAR, People's Republic of China.
authors.forename: Han-Sung
authors.initials: HS
authors.lastname: Jung
mesh_terms: D000199:Actins / Q000378:metabolism; D022005:Adherens Junctions / Q000378:metabolism; D000818:Animals; D049109:Cell Proliferation; D004848:Epithelium / Q000502:physiology; D005353:Fibronectins / Q000378:metabolism; D005849:Gerbillinae; D051741:Kruppel-Like Transcription Factors / Q000235:genetics; D008813:Mice, Inbred ICR; D018345:Mice, Knockout; D008963:Molar / Q000033:anatomy & histology* / Q000166:cytology / Q000196:embryology / Q000378:metabolism; D009479:Neuropeptides / Q000378:metabolism; D009924:Organ Culture Techniques; D013045:Species Specificity; D020830:rac1 GTP-Binding Protein / Q000235:genetics / Q000378:metabolism*; D020741:rho GTP-Binding Proteins / Q000378:metabolism; D020742:rhoA GTP-Binding Protein / Q000235:genetics / Q000378:metabolism*
chemical_list: D000199:Actins; D005353:Fibronectins; D051741:Kruppel-Like Transcription Factors; D009479:Neuropeptides; C484602:Rac1 protein, mouse; C498818:Sp6 protein, mouse; C526380:RhoA protein, mouse; D020830:rac1 GTP-Binding Protein; D020741:rho GTP-Binding Proteins; D020742:rhoA GTP-Binding Protein