Difference between revisions of "Integumentary System - Tooth Development"

From Embryology
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| {{Mouse tooth movie 1}}
| {{Mouse tooth movie 1}}
| 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.<ref name="PMID27588418"><pubmed>27588418</pubmed></ref> The tooth germ is from a developing molar and the lingual side is on the left.
| valign=top|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.<ref name="PMID27588418"><pubmed>27588418</pubmed></ref>  
The tooth germ is from a developing molar and the lingual side is on the left.
== Development Overview ==
== Development Overview ==

Revision as of 15:53, 1 August 2017

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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.

lamina placode bud cap bell
lamina placode stage bud stage cap stage bell stage

Links: Gastrointestinal Tract Development

Integumentary Links: integumentary | Lecture | hair | tooth | nail | integumentary gland | mammary gland | vernix caseosa | melanocyte | touch | Eyelid | outer ear | Histology | integumentary abnormalities | Category:Integumentary
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Historic Embryology - Integumentary  
1906 Papillary ridges | 1910 Manual of Human Embryology | 1914 Integumentary | 1923 Head Subcutaneous Plexus | 1921 Text-Book of Embryology | 1924 Developmental Anatomy | 1941 Skin Sensory | Historic Disclaimer
Historic Tooth Development  
1902 Tooth Development | 1912 The Teeth | 1921 The Teeth

Some Recent Findings

Neonatal rat teeth
  • Review - PAX9 gene mutations and tooth agenesis[1] "Paired box 9 (PAX9) is one of the best-known transcription factors involved in the development of human dentition. Mutations in PAX9 gene could, therefore, seriously influence the number, position and morphology of the teeth in an affected individual. To date, over 50 mutations in the gene have been reported as associated with various types of dental agenesis (congenitally missing teeth) and other inherited dental defects or variations. The most common consequence of PAX9 gene mutation is the autosomal-dominant isolated (non-syndromic) oligodontia or hypodontia. In the present review, we are summarizing all known PAX9 mutations as well as their nature and precise loci in the DNA sequence of the gene." Pax
  • Epithelial stratification and placode invagination are separable functions in early morphogenesis of the molar tooth[2] "Ectodermal organs, which include teeth, hair follicles, mammary ducts, and glands such as sweat, mucous and sebaceous glands, are initiated in development as placodes, which are epithelial thickenings that invaginate and bud into the underlying mesenchyme. These placodes are stratified into a basal and several suprabasal layers of cells. The mechanisms driving stratification and invagination are poorly understood. ...We present a model in which FGF generates suprabasal tissue by asymmetric cell division, while Shh triggers cell rearrangement in this tissue to drive invagination all the way to bud formation."
  • Fate of HERS during tooth root development.[3] "Tooth root development begins after the completion of crown formation in mammals. Previous studies have shown that Hertwig's epithelial root sheath (HERS) plays an important role in root development, but the fate of HERS has remained unknown. In order to investigate the morphological fate and analyze the dynamic movement of HERS cells in vivo, we generated K14-Cre;R26R mice. HERS cells are detectable on the surface of the root throughout root formation and do not disappear. Most of the HERS cells are attached to the surface of the cementum, and others separate to become the epithelial rest of Malassez. HERS cells secrete extracellular matrix components onto the surface of the dentin before dental follicle cells penetrate the HERS network to contact dentin. HERS cells also participate in the cementum development and may differentiate into cementocytes. During root development, the HERS is not interrupted, and instead the HERS cells continue to communicate with each other through the network structure. Furthermore, HERS cells interact with cranial neural crest derived mesenchyme to guide root development. Taken together, the network of HERS cells is crucial for tooth root development."
  • Expression survey of genes critical for tooth development in the human embryonic tooth germ.[4] "examined the expression patterns of several regulatory genes, including BMP4, FGF8, MSX1, PAX9, PITX2, and SHOX2, and compared them with that found in mice. ...results indicate that, although slight differences exist in the gene expression patterns, the human and mouse teeth not only share considerable homology in odontogenesis but also use similar underlying molecular networks."
More recent papers  
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Search term: Tooth Embryology

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  • 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


 ‎‎Tooth E12.5-17
Page | Play
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.[5]

The tooth germ is from a developing molar and the lingual side is on the left.

Development Overview

  • 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

Tooth Stages

Tooth development stages[6]
lamina lamina Week 6 E 11
placode placode stage Week 7 E 11.5
bud bud stage Week 8 E 12.5
cap cap stage Week 11 E 14.5
bell bell stage Week 14 E 15.5
Tooth Stages  
lamina lamina Week 6 E11
placode placode stage Week 7 E11.5
bud bud stage Week 8 E12.5
cap cap stage Week 11 E14.5
bell bell stage Week 14 E15.5

Image Links: all stages | lamina | placode stage | bud stage | cap stage | bell stage

Human 2 Sets of Teeth

Human permanent teeth appearance (eruption)

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
Source: The Teeth (1912)[7]

Deciduous Teeth

  • 20 deciduous teeth
  • Differential rates of growth, shed at different times over 20 year period

Deciduous teeth

Permanent Teeth

Human adult mandibular teeth pattern
  • 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.

Permanent teeth

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)

Periodontal Ligament

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

Tooth molecular development[6]

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.[8]

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.[9]

Foxi3 forkhead-box transcription factor inhibits formation of enamel knots and cervical loops and therefore the differentiation of dental epithelium.[10]


Inherited dentine disorders[11]


A total lack of tooth development.

Dentinogenesis imperfecta

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)

Dentine dysplasia

The primary teeth are translucent and amber in colour whereas the erupting secondary central incisors are of normal appearance.

Amelogenesis Imperfecta

Abnormal tooth enamel formation (AMELX, ENAM, KLK4, MMP20).

Dens Evaginatus

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.


Small teeth.

Hutchinson's teeth

(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.

Links: Abnormal Development - Syphilis


  1. <pubmed>28155232</pubmed>
  2. <pubmed>26755699</pubmed>
  3. <pubmed>19576204</pubmed>
  4. <pubmed>17394220</pubmed>
  5. <pubmed>27588418</pubmed>
  6. 6.0 6.1 <pubmed>19266065</pubmed>| PMCID: PMC2651620
  7. Manual of Human Embryology II Keibel, F. and Mall, F.P. J. B. Lippincott Company, Philadelphia (1912)
  8. <pubmed>16651263</pubmed>
  9. <pubmed>26487719</pubmed>
  10. <pubmed>26450968</pubmed>
  11. <pubmed>19021896</pubmed>



<pubmed>24495023</pubmed> <pubmed>19875280</pubmed> <pubmed>17209531</pubmed> <pubmed>16838332</pubmed> <pubmed>16753804</pubmed> <pubmed>12615136</pubmed> <pubmed>12640730</pubmed>


<pubmed>17394220</pubmed> <pubmed>16632755</pubmed> <pubmed>16651263</pubmed> <pubmed>9520113</pubmed>

Search PubMed

Search Pubmed: Tooth Development | odontogenesis | tooth morphogenesis | adontia | amelogenesis imperfecta | dens evaginatus | hypodontia

Additional Images

Category:Tooth | Category:Integumentary


Development and Morphology of the Teeth (1902)

The Teeth (1912)

The Teeth (1921)


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Cite this page: Hill, M.A. (2021, September 22) Embryology Integumentary System - Tooth Development. Retrieved from https://embryology.med.unsw.edu.au/embryology/index.php/Integumentary_System_-_Tooth_Development

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© Dr Mark Hill 2021, UNSW Embryology ISBN: 978 0 7334 2609 4 - UNSW CRICOS Provider Code No. 00098G