Twist1 Is Essential for Tooth Morphogenesis and Odontoblast Differentiation.
Twist1 is a basic helix-loop-helix-containing transcription factor that is expressed in the dental mesenchyme during the early stages of tooth development. To better delineate its roles in tooth development, we generated Twist1 conditional knockout embryos (Twist2(Cre) (/+);Twist1(fl/fl)) by breeding Twist1 floxed mice (Twist1(fl/fl)) with Twist2-Cre recombinase knockin mice (Twist2(Cre) (/+)). The Twist2(Cre) (/+);Twist1(fl/fl) embryos formed smaller tooth germs and abnormal cusps during early tooth morphogenesis. Molecular and histological analyses showed that the developing molars of the Twist2(Cre) (/+);Twist1(fl/fl) embryos had reduced cell proliferation and expression of fibroblast growth factors 3, 4, 9, and 10 and FGF receptors 1 and 2 in the dental epithelium and mesenchyme. In addition, 3-week-old renal capsular transplants of embryonic day 18.5 Twist2(Cre) (/+);Twist1(fl/fl) molars showed malformed crowns and cusps with defective crown dentin and enamel. Immunohistochemical analyses revealed that the implanted mutant molars had defects in odontoblast differentiation and delayed ameloblast differentiation. Furthermore, in vitro ChIP assays demonstrated that Twist1 was able to bind to a specific region of the Fgf10 promoter. In conclusion, our findings suggest that Twist1 plays crucial roles in regulating tooth development and that it may exert its functions through the FGF signaling pathway.
From the Department of Biomedical Sciences and Center for Craniofacial Research and Diagnosis, Texas A&M University Baylor College of Dentistry, Dallas, Texas 75246, the State Key Laboratory of Oral Diseases and Department of Cleft Lip and Palate Surgery, West China Hospital of Stomatology, Sichuan University, Chengdu 610041, China.
Tian
T
Meng
From the Department of Biomedical Sciences and Center for Craniofacial Research and Diagnosis, Texas A&M University Baylor College of Dentistry, Dallas, Texas 75246, the Guanghua School of Stomatology, Hospital of Stomatology, Sun Yat-sen University, Guangzhou 510055, China, and.
Yanyu
Y
Huang
From the Department of Biomedical Sciences and Center for Craniofacial Research and Diagnosis, Texas A&M University Baylor College of Dentistry, Dallas, Texas 75246.
Suzhen
S
Wang
From the Department of Biomedical Sciences and Center for Craniofacial Research and Diagnosis, Texas A&M University Baylor College of Dentistry, Dallas, Texas 75246.
Hua
H
Zhang
From the Department of Biomedical Sciences and Center for Craniofacial Research and Diagnosis, Texas A&M University Baylor College of Dentistry, Dallas, Texas 75246.
Paul C
PC
Dechow
From the Department of Biomedical Sciences and Center for Craniofacial Research and Diagnosis, Texas A&M University Baylor College of Dentistry, Dallas, Texas 75246.
Xiaofang
X
Wang
From the Department of Biomedical Sciences and Center for Craniofacial Research and Diagnosis, Texas A&M University Baylor College of Dentistry, Dallas, Texas 75246.
Chunlin
C
Qin
the State Key Laboratory of Oral Diseases and Department of Cleft Lip and Palate Surgery, West China Hospital of Stomatology, Sichuan University, Chengdu 610041, China.
Bing
B
Shi
the University of Utah Health Sciences, Salt Lake City, Utah 84112 rena.dsouza@hsc.utah.edu.
Rena N
RN
D'Souza
From the Department of Biomedical Sciences and Center for Craniofacial Research and Diagnosis, Texas A&M University Baylor College of Dentistry, Dallas, Texas 75246, ylu@bcd.tamhsc.edu.
Yongbo
Y
Lu
D000818:Animals; D002356:Cartilage / Q000502:physiology; D002454:Cell Differentiation; D049109:Cell Proliferation; D002478:Cells, Cultured; D003433:Crosses, Genetic; D005260:Female; D018507:Gene Expression Regulation, Developmental; D055879:Gene Knock-In Techniques; D051379:Mice; D008810:Mice, Inbred C57BL; D009024:Morphogenesis / Q000502:physiology*; D009687:Nuclear Proteins / Q000235:genetics / Q000502:physiology*; D009804:Odontoblasts / Q000502:physiology*; D011401:Promoter Regions, Genetic; D011485:Protein Binding; D012097:Repressor Proteins / Q000235:genetics; D015398:Signal Transduction; D014070:Tooth / Q000196:embryology* / Q000502:physiology; D014083:Tooth Germ / Q000502:physiology; D051879:Twist-Related Protein 1 / Q000235:genetics / Q000502:physiology*; D055114:X-Ray Microtomography
D009687:Nuclear Proteins; D012097:Repressor Proteins; D051879:Twist-Related Protein 1; C096852:Twist2 protein, mouse; C067250:Twist1 protein, mouse
Twist1; Twist2; cell differentiation; dentin; enamel formation; odontoblast differentiation; tooth; tooth development; tooth morphogenesis; transplantation