Integumentary System - Tooth Development
|Embryology - 17 Nov 2017 Expand to Translate|
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- 1 Introduction
- 2 Some Recent Findings
- 3 Textbooks
- 4 Movies
- 5 Development Overview
- 6 Tooth Stages
- 7 Human 2 Sets of Teeth
- 8 Epithelial Mesenchymal Interaction
- 9 Periodontal Ligament
- 10 Molecular Tooth Development
- 11 Abnormalities
- 12 References
- 13 Additional Images
- 14 Terms
- 15 External Links
- 16 Glossary Links
The tooth is an extrordinary integumentary system specialization providing insights into epitheilal/mesenchymal (ectoderm of the first pharyngeal arch and neural crest, ectomesenchymal cells) interactions in development and has a major contribution from the neural crest. (More? Neural Crest Development)
There are 4 morphological stages describing the early tooth development: bud, cap, bell, and terminal differentiation.
|Historic Tooth Development|
|1902 Tooth Development | 1912 The Teeth | 1921 The Teeth|
Some Recent Findings
|More recent papers|
This table shows an automated computer PubMed search using the listed sub-heading term.
References listed on the rest of the content page and the associated discussion page (listed under the publication year sub-headings) do include some editorial selection based upon both relevance and availability.
S Rehrl, W Schröder, C Müller, C Staszyk, C Lischer Radiological prevalence of equine odontoclastic tooth resorption and hypercementosis. Equine Vet. J.: 2017; PubMed 29067719
Roberta De Mori, Marta Romani, Stefano D'Arrigo, Maha S Zaki, Elisa Lorefice, Silvia Tardivo, Tommaso Biagini, Valentina Stanley, Damir Musaev, Joel Fluss, Alessia Micalizzi, Sara Nuovo, Barbara Illi, Luisa Chiapparini, Lucia Di Marcotullio, Mahmoud Y Issa, Danila Anello, Antonella Casella, Monia Ginevrino, Autumn Sa'na Leggins, Susanne Roosing, Romina Alfonsi, Jessica Rosati, Rachel Schot, Grazia Maria Simonetta Mancini, Enrico Bertini, William B Dobyns, Tommaso Mazza, Joseph G Gleeson, Enza Maria Valente Hypomorphic Recessive Variants in SUFU Impair the Sonic Hedgehog Pathway and Cause Joubert Syndrome with Cranio-facial and Skeletal Defects. Am. J. Hum. Genet.: 2017; PubMed 28965847
Darko Kero, Katarina Vukojevic, Petra Stazic, Danijela Sundov, Snjezana Mardesic Brakus, Mirna Saraga-Babic Regulation of proliferation in developing human tooth germs by MSX muscle segment homeodomain proteins and cyclin-dependent kinase inhibitor p19(INK4d). Organogenesis: 2017; PubMed 28933666
J M Richman, B C Schutte Face Forward: Gene Variants, Pathways, and Therapies for Craniofacial Anomalies. J. Dent. Res.: 2017, 96(11);1181-1183 PubMed 28929929
Lucas L Boer, Jana Naue, Laurens de Rooy, Roelof-Jan Oostra Detection of G1138A Mutation of the FGFR3 Gene in Tooth Material from a 180-Year-Old Museological Achondroplastic Skeleton. Genes (Basel): 2017, 8(9); PubMed 28850094
- Human Embryology (2nd ed.) Larson Chapter 14 p443-455
- The Developing Human: Clinically Oriented Embryology (6th ed.) Moore and Persaud Chapter 20: P513-529
- Before We Are Born (5th ed.) Moore and Persaud Chapter 21: P481-496
- Essentials of Human Embryology Larson Chapter 14: P303-315
- Human Embryology, Fitzgerald and Fitzgerald
- Color Atlas of Clinical Embryology Moore Persaud and Shiota Chapter 15: p231-236
|This time-lapse movie from a mouse embryo (E 12.5–13.5) cultured for 5 days ex vivo, images were taken at 30-min intervals.
The tooth germ is from a developing molar and the lingual side is on the left.
- ectoderm, mesoderm and neural crest ectomesenchyme contribute
- inductive influence of neural crest with overlying ectoderm
- neural crest-derived mesenchymal cells
- differentiate under the influence of the enamel epithelium
- form predentin
- calcifies to form dentin
- produce enamal
- tooth growth occurs in ossifying jaws
- periodontal ligament holds tooth in bone socket
|lamina||Week 6||E 11|
|placode||Week 7||E 11.5|
|bud||Week 8||E 12.5|
|cap||Week 11||E 14.5|
|bell||Week 14||E 15.5|
Human 2 Sets of Teeth
Human Dentition Timeline
|The milk dentition|
|Median incisors||6th to 8th month|
|Lateral incisors||8th to 12th month|
|First molars||12th to 16th month|
|Canines 1||7th to 20th month|
|Second molars||20th to 24th month|
|The permanent dentition|
|First molars||7th year|
|Median incisors||8th year|
|Lateral incisors||9th year|
|First premolars||10th year|
|Second premolars||11th year|
|Canines||13th to 14th year|
|Second molars||13th to 14th year|
|Third molars||17th to 40th year|
- 20 deciduous teeth
- Differential rates of growth, shed at different times over 20 year period
- 32 permanent teeth
- Incisors - sharp cutting edge, adapted for biting the food.
- Canines - are larger and stronger than the incisors. The upper canines have also been called the "eye teeth", while the lower canines "stomach teeth".
- Premolars - or Bicuspid teeth are smaller and shorter than the canines.
- Molars - are the largest teeth adapted for grinding and pounding food.
Epithelial Mesenchymal Interaction
local ectodermal thickening expresses several signaling molecules these in turn signal to the underlying mesenchyme triggering mesenchymal condensation (epithelially expressed Bmp4 induces Msx1 and Lef1 as well as itself in the underlying mesenchyme)
Four epithelial signaling molecules, Bmp2, Shh, Wnt10a, and Wnt10b, in the early inductive cascade, each signal has a distinct molecular action on the jaw mesenchyme.
Mouse (E11.0 and E12.0) - all four genes are specifically expressed in the epithelium.
Shh and Wnt10b induce general Hedgehog and Wnt targets, Ptc and Gli for Shh and Lef1 for Wnt10b,
Bmp2 is able to induce tooth-specific expression of Msx1.
(Text above modified from: Hélène R. Dassule and Andrew P. McMahon Developmental Biology, v 202, n 2, October 15, 1998, p215-227)
(More? Developmental Mechanism - Epithelial Mesenchymal Interaction)
The tooth is not anchored directly onto its bony socket (alveolar bone) but held in place by the periodontal ligament (PDL), a specialized connective tissue structure that surrounds the tooth root coating of cementum.
The additional roles of the PDL are to also act as; a shock absorber, transmitter of chewing forces (from tooth to bone), sensory information (heat, cold, pressure and pain).
The collagen fiber bundles within the ligament are called "Sharpey’s fibres".
Cementum (from investing layer of the dental follicle) is contiguous layer with the periodontal ligament on one surface and firmly adherent to dentine on the other surface.
Molecular Tooth Development
More than 300 genes have been associated with tooth development including: BMP4, FGF8, MSX1, MSX2, PAX9, PITX2, SHOX2, Delta/Notch, Hox-8, Runx2
Most recent review in Developmental Dynamics by Lin D, Huang Y, He F, Gu S, Zhang G, Chen Y, Zhang Y. Expression survey of genes critical for tooth development in the human embryonic tooth germ. Dev Dyn. 2007 Mar 29.
Amelogenin - abundant protein secreted by ameloblasts which is a major component of tooth enamel.
The papers below are from UNSW Embryology (version 3), information requires updating.
Bone Morphogenic Protein (BMP) / Fibroblast Growth Factor (FGF)
Growth factors in the BMP- and FGF-families are expressed in dental epithelium during initiation of tooth development and their effects on the underlying mesenchyme mimic those of the epithelium. They upregulate the expression of many genes, including the homeobox-containing Msx-1 and Msx-2, and stimulate cell proliferation suggesting that they may act as epithelial signals transmitting epithelial-mesenchymal interactions. During subsequent morphogenesis, when the characteristic shapes of individual teeth develop as a result from folding of the dental epithelium, several signal molecules including Sonic hedgehog, Bmps-2, 4, 7 and Fgf-4 are expressed specifically in restricted and transient epithelial cell clusters, called enamel knots.
(Text: Irma Thesleff and Carin Sahlberg Seminars in Cell & Developmental Biology, v 7, n 2, April, 1996, p185-193)
The expression pattern of Delta 1 in ameloblasts and odontoblasts is complementary to Notch1, Notch2, and Notch3 expression in adjacent epithelial and mesenchymal cells. Notch1 and Notch2 are upregulated in explants of dental mesenchyme adjacent to implanted cells expressing Delta1, suggesting that feedback regulation by Delta-Notch signaling ensures the spatial segregation of Notch receptors and ligands. TGF1 and BMPs induce Delta1 expression in dental mesenchyme explants at the stage at which Delta1 is upregulated in vivo, but not at earlier stages. In contrast to the Notch family receptors and their ligand Jagged1, expression of Delta1 in the tooth germ is not affected by epithelial-mesenchymal interactions, showing that the Notch receptors and their two ligands Jagged1 and Delta1 are subject to different regulations.
Text: Mitsiadis etal Developmental Biology,v 204, n 2, December 15, 1998, p420-431
Bmp4 expression by the interaction of Pax9 with Msx1 at the level of transcription and protein complex determines the fate of the transition from bud to cap stage during tooth development.
Twist1 a basic helix-loop-helix-containing transcription factor expressed in dental mesenchyme during the early stages of tooth development acts through the FGF signaling pathway.
Foxi3 forkhead-box transcription factor inhibits formation of enamel knots and cervical loops and therefore the differentiation of dental epithelium.
A total lack of tooth development.
The teeth are translucent and often roughened with severe amber discolouration. Discoloured teeth with an opalescent sheen, dentin does not support enamel (dentin sialophosphoprotein mutation)
The primary teeth are translucent and amber in colour whereas the erupting secondary central incisors are of normal appearance.
Abnormal tooth enamel formation (AMELX, ENAM, KLK4, MMP20).
Dental anomaly mainly affecting premolars in people of Mongolian origin.
Lack of development of one or more teeth.
Hypohidrotic Ectodermal Dysplasia
Maldevelopment of one or more ectodermal-derived tissues.
(Hutchinson's incisor, Hutchinson's sign, Hutchinson-Boeck teeth) Historic clinical term for an infant tooth abnormality associated with congenital syphilis. Teeth are smaller, more widely spaced than normal and have notches on the biting surfaces. Named after Jonathan Hutchinson (1828 – 1913) an English surgeon and pathologist, who first described this association.
- Ondřej Bonczek, Vladimir J Balcar, Omar Šerý PAX9 gene mutations and tooth agenesis: a review. Clin. Genet.: 2017; PubMed 28155232
- Jingjing Li, Lemonia Chatzeli, Eleni Panousopoulou, Abigail S Tucker, Jeremy B A Green Epithelial stratification and placode invagination are separable functions in early morphogenesis of the molar tooth. Development: 2016; PubMed 26755699
- Xiaofeng Huang, Pablo Bringas, Harold C Slavkin, Yang Chai Fate of HERS during tooth root development. Dev. Biol.: 2009, 334(1);22-30 PubMed 19576204
- Dahe Lin, Yide Huang, Fenglei He, Shuping Gu, Guozhong Zhang, YiPing Chen, Yanding Zhang Expression survey of genes critical for tooth development in the human embryonic tooth germ. Dev. Dyn.: 2007, 236(5);1307-12 PubMed 17394220
- Ritsuko Morita, Miho Kihira, Yousuke Nakatsu, Yohei Nomoto, Miho Ogawa, Kazumasa Ohashi, Kensaku Mizuno, Tetsuhiko Tachikawa, Yukitaka Ishimoto, Yoshihiro Morishita, Takashi Tsuji Coordination of Cellular Dynamics Contributes to Tooth Epithelium Deformations. PLoS ONE: 2016, 11(9);e0161336 PubMed 27588418
- Despina S Koussoulakou, Lukas H Margaritis, Stauros L Koussoulakos A curriculum vitae of teeth: evolution, generation, regeneration. Int. J. Biol. Sci.: 2009, 5(3);226-43 PubMed 19266065 | PMCID: PMC2651620
- Manual of Human Embryology II Keibel, F. and Mall, F.P. J. B. Lippincott Company, Philadelphia (1912)
- Takuya Ogawa, Hitesh Kapadia, Jian Q Feng, Rajendra Raghow, Heiko Peters, Rena N D'Souza Functional consequences of interactions between Pax9 and Msx1 genes in normal and abnormal tooth development. J. Biol. Chem.: 2006, 281(27);18363-9 PubMed 16651263
- Tian Meng, Yanyu Huang, Suzheng Wang, Hua Zhang, Paul C Dechow, Xiaofang Wang, Chunlin Qin, Bing Shi, Rena N D'Souza, Yongbo Lu Twist1 is Essential for Tooth Morphogenesis and Odontoblast Differentiation. J. Biol. Chem.: 2015; PubMed 26487719
- Maria Jussila, Anne Aalto, Maria Sanz Navarro, Vera Shirokova, Anamaria Balic, Aki Kallonen, Takahiro Ohyama, Andrew Groves, Marja L Mikkola, Irma Thesleff Suppression of epithelial differentiation by Foxi3 is essential for molar crown patterning. Development: 2015; PubMed 26450968
- Martin J Barron, Sinead T McDonnell, Iain Mackie, Michael J Dixon Hereditary dentine disorders: dentinogenesis imperfecta and dentine dysplasia. Orphanet J Rare Dis: 2008, 3;31 PubMed 19021896
R Peterkova, M Hovorakova, M Peterka, H Lesot Three-dimensional analysis of the early development of the dentition. Aust Dent J: 2014, 59 Suppl 1;55-80 PubMed 24495023
Marianna Bei Molecular genetics of tooth development. Curr. Opin. Genet. Dev.: 2009, 19(5);504-10 PubMed 19875280
Maisa Seppala, Maria Zoupa, Obinna Onyekwelu, Martyn T Cobourne Tooth development: 1. Generating teeth in the embryo. Dent Update: 2006, 33(10);582-4, 586-8, 590-1 PubMed 17209531
Irma Thesleff The genetic basis of tooth development and dental defects. Am. J. Med. Genet. A: 2006, 140(23);2530-5 PubMed 16838332
Kevin Tompkins Molecular mechanisms of cytodifferentiation in mammalian tooth development. Connect. Tissue Res.: 2006, 47(3);111-8 PubMed 16753804
Martyn T Cobourne, Paul T Sharpe Tooth and jaw: molecular mechanisms of patterning in the first branchial arch. Arch. Oral Biol.: 2003, 48(1);1-14 PubMed 12615136
P T Sharpe Neural crest and tooth morphogenesis. Adv. Dent. Res.: 2001, 15;4-7 PubMed 12640730
Dahe Lin, Yide Huang, Fenglei He, Shuping Gu, Guozhong Zhang, YiPing Chen, Yanding Zhang Expression survey of genes critical for tooth development in the human embryonic tooth germ. Dev. Dyn.: 2007, 236(5);1307-12 PubMed 17394220
M Nakatomi, I Morita, K Eto, M S Ota Sonic hedgehog signaling is important in tooth root development. J. Dent. Res.: 2006, 85(5);427-31 PubMed 16632755
Takuya Ogawa, Hitesh Kapadia, Jian Q Feng, Rajendra Raghow, Heiko Peters, Rena N D'Souza Functional consequences of interactions between Pax9 and Msx1 genes in normal and abnormal tooth development. J. Biol. Chem.: 2006, 281(27);18363-9 PubMed 16651263
P Kettunen, I Thesleff Expression and function of FGFs-4, -8, and -9 suggest functional redundancy and repetitive use as epithelial signals during tooth morphogenesis. Dev. Dyn.: 1998, 211(3);256-68 PubMed 9520113
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- StemBook - Tooth organogenesis and regeneration
- University of Helsinki Gene Expression in Tooth
- American Dental Association Overview - Tooth
- Columbia University Medical Centre Illustrations: How a Tooth Decays
- Merck Tooth disorders
- Nemours Foundation Teething Tots
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Cite this page: Hill, M.A. 2017 Embryology Integumentary System - Tooth Development. Retrieved November 17, 2017, from https://embryology.med.unsw.edu.au/embryology/index.php/Integumentary_System_-_Tooth_Development
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