Integumentary System - Tooth Development: Difference between revisions

From Embryology
mNo edit summary
mNo edit summary
 
(37 intermediate revisions by the same user not shown)
Line 1: Line 1:
{{Header}}
{{Header}}
== Introduction ==
== Introduction ==
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]])
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.
After placed formation, there are four key morphological stages describing the early tooth development: bud, cap, bell, and terminal differentiation.


{{tooth stages table}}
{{tooth stages table}}
Recent molecular animal model studies have shown that epithelial {{Wnt}}/β-catenin signaling is sufficient to initiate tooth development through activating {{Shh}}, {{Bmp}}s, {{Fgf}}s and {{Wnt}}s in the dental epithelium.{{#pmid:30570432|PMID30570432}} This then initiates the expression of odontogenic genes in the underlying mesenchyme.


<br>
<br>
 
{{Tooth Vignette}}
 
<br>
'''Links:''' [[Gastrointestinal Tract Development]]
'''Links:''' {{Gastrointestinal tract}}
 
<br>
{{Integumentary Links}}
{{Integumentary Links}}


{| class="wikitable mw-collapsible mw-collapsed"
{| class="wikitable mw-collapsible mw-collapsed"
! [[Embryology_History|'''Historic''']] Tooth Development &nbsp;  
! [[Historic Embryology Papers|'''Historic''']] Tooth Development &nbsp;  
|-
|-
| [[Book_-_Human_Embryology_and_Morphology_5|1902 Tooth Development]] | [[Book_-_Manual_of_Human_Embryology_17-2#The_Teeth|1912 The Teeth]] | [[Book_-_Text-Book_of_Embryology_12#The_Teeth|1921 The Teeth]]
| [[Book_-_Human_Embryology_and_Morphology_5|1902 Tooth Development]] | [[Book_-_Manual_of_Human_Embryology_17-2#The_Teeth|1912 The Teeth]] | [[Book_-_Text-Book_of_Embryology_12#The_Teeth|1921 The Teeth]]
|}
|}
== Some Recent Findings ==
== Some Recent Findings ==
[[File:Rat-neonatal_teeth.jpg|thumb|Neonatal rat teeth]]
[[File:Tooth eruption signaling.jpg|thumb|Tooth eruption signaling{{#pmid:30602459|PMID30602459}}]]
{|
{|
|-bgcolor="F5FAFF"  
|-bgcolor="F5FAFF"  
|
|
* Review - '''PAX9 gene mutations and tooth agenesis'''<ref name="PMID28155232"><pubmed>28155232</pubmed></ref> "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." [[Developmental Signals - Pax|Pax]]
 
* '''Epithelial stratification and placode invagination are separable functions in early morphogenesis of the molar tooth'''<ref name="PMID26755699"><pubmed>26755699</pubmed></ref> "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."
* '''Immortalized Hertwig's epithelial root sheath cell line works as model for epithelial-mesenchymal interaction during tooth root formation'''{{#pmid:31512758|PMID31512758}} "Hertwig's epithelial root sheath (HERS) is critical for epithelial-mesenchymal interaction (EMI) during tooth root formation. However, the exact roles of HERS in odontogenic differentiation by EMI have not been well characterized, because primary HERS cells are difficult to obtain. Immortalized cell lines constitute crucial scientific tools, while there are few HERS cell lines available. Our previous study has successfully established immortalized HERS cell lines. Here, we confirmed the phenotype of our HERS-H1 by verifying its characteristics and functions in odontogenic differentiation through EMI. The HERS-H1-conditioned medium (CM-H1) effectively enhanced odontogenic differentiation of dental papilla cells (DPCs) in vitro. Furthermore, Smad4 and p-Smad1/5/8 were significantly activated in DPCs treated with CM-H1, and this activation was attenuated by noggin. In vivo, our implanted recombinants of HERS-H1 and DPCs exhibited mineralized tissue formation and expression of Smad4, p-Smad1/5/8, and odontogenic differentiation markers. Our results indicated that HERS-H1 promoted DPCs odontoblastic differentiation via bone morphogenetic protein/Smad signaling. HERS-H1 exhibits relevant key molecular characteristics and constitutes a new biological model for basic research on HERS and the dental EMI during root development and regeneration."
* '''Fate of HERS during tooth root development.'''<ref name="PMID19576204"><pubmed>19576204</pubmed></ref> "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.'''<ref><pubmed>17394220</pubmed></ref> "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."
* '''Parathyroid hormone-related peptide (1-34) promotes tooth eruption and inhibits osteogenesis of dental follicle cells during tooth development'''{{#pmid:30584670|PMID30584670}} "Dental follicle cells (DFCs) activate and recruit osteoclasts for tooth development and tooth eruption, whereas DFCs themselves differentiate into osteoblasts to form alveolar bone surrounding tooth roots through the interaction with Hertwig's epithelial root sheath (HERS). Also during tooth development, parathyroid hormone-related peptide (PTHrP) is expressed surrounding the tooth germ. Thus, we aimed to investigate the effect of PTHrP (1-34) on bone resorption and osteogenesis of DFCs in vitro and in vivo. In vitro studies demonstrated that DFCs cocultured with HERS cells expressed higher levels of BSP and OPN than the DFCs control group, whereas cocultured DFCs treated with PTHrP (1-34) had lower expressions of ALP, RUNX2, BSP, and OPN than the cocultured DFCs control group. Moreover, we found PTHrP (1-34) inhibited osteogenesis of cocultured DFCs by inactivating the Wnt/β-catenin pathway. PTHrP (1-34) also increased the expression of RANKL/OPG ratio in DFCs. Consistently, in vivo study found that PTHrP (1-34) accelerated tooth eruption and inhibited alveolar bone formation. Therefore, these results suggest that PTHrP (1-34) accelerates tooth eruption and inhibits osteogenesis of DFCs by inactivating Wnt/β-catenin pathway."
 
* '''Autocrine regulation of mesenchymal progenitor cell fates orchestrates tooth eruption'''{{#pmid:30509999|PMID30509999}} "Formation of functional skeletal tissues requires highly organized steps of mesenchymal progenitor cell differentiation. The dental follicle (DF) surrounding the developing tooth harbors mesenchymal progenitor cells for various differentiated cells constituting the tooth root–bone interface and coordinates tooth eruption in a manner dependent on signaling by parathyroid hormone-related peptide (PTHrP) and the PTH/PTHrP receptor (PPR). However, the identity of mesenchymal progenitor cells in the DF and how they are regulated by PTHrP-PPR signaling remain unknown. Here, we show that the PTHrP-PPR autocrine signal maintains physiological cell fates of DF mesenchymal progenitor cells to establish the functional periodontal attachment apparatus and orchestrates tooth eruption. A single-cell RNA-seq analysis revealed cellular heterogeneity of PTHrP+ cells, wherein PTHrP+ DF subpopulations abundantly express PPR. Cell lineage analysis using tamoxifen-inducible PTHrP-creER mice revealed that PTHrP+ DF cells differentiate into cementoblasts on the acellular cementum, periodontal ligament cells, and alveolar cryptal bone osteoblasts during tooth root formation. PPR deficiency induced a cell fate shift of PTHrP+ DF mesenchymal progenitor cells to nonphysiological cementoblast-like cells precociously forming the cellular cementum on the root surface associated with up-regulation of Mef2c and matrix proteins, resulting in loss of the proper periodontal attachment apparatus and primary failure of tooth eruption, closely resembling human genetic conditions caused by PPR mutations."
 
* '''Persistent Wnt/β-catenin signaling in mouse epithelium induces the ectopic Dspp expression in cheek mesenchyme'''{{#pmid:30570432|PMID30570432}} "Tooth development is accomplished by a series of epithelial-mesenchyme interactions. Epithelial Wnt/β-catenin signaling is sufficient to initiate tooth development by activating Shh, Bmps, Fgfs and Wnts in dental epithelium, which in turn, triggered the expression of odontogenic genes in the underlying mesenchyme. Although constitutive activation of Wnt/β-catenin signaling in oral ectoderm resulted in the continuous tooth formation throughout the life span, if the epithelial Wnt/β-catenin signaling could induce the mesenchyme other than oral mesenchyme still required to be elucidated. In this study, we found that in the K14-cre; Ctnnb1ex3f mice, the markers of dental epithelium, such as Pitx2, Shh, Bmp2, Fgf4, and Fgf8, were not only activated in the oral ectoderm, but also in the cheek epithelium. Surprisingly, the underlying cheek mesenchymal cells were elongated and expressed Dspp. Further investigations detected that the expression of Msx1 and Runx2 extended from oral to cheek mesenchyme. These findings suggested that epithelial Wnt/β-catenin signaling was capable of inducing Dspp expression in non-dental mesenchyme. ...In summary, our findings suggested that the epithelial Wnt/β-catenin signaling could induce craniofacial mesenchyme into odontogenic program and promote odontoblast differentiation.
 
* '''Upstream Enhancer Elements of Shh Regulate Oral and Dental Patterning'''{{#pmid:29481312|PMID29481312}} "Sonic hedgehog ( Shh) is important in pattern formation during development. Shh transcription is modulated by a long-range regulatory mechanism containing a number of enhancers, which are spread over nearly 850 kb in the mouse genome. Shh enhancers in the nervous system have been found between intron and 430 kb upstream of Shh. Enhancers in the oral cavity, pharynx, lung, gut, and limbs have been discovered between 610 kb and 850 kb upstream of Shh. However, the intergenic region ranging from 430 to 610 kb upstream of Shh remains to be elucidated. In the present study, we found a novel long-range enhancer located 558 kb upstream of Shh. The enhancer showed in vivo activity in oral cavity and whiskers. A targeted deletion from the novel enhancer to mammal reptile conserved sequence 1 (MRCS1), which is a known enhancer of Shh in oral cavity, resulted in supernumerary molar formation, confirming the essential role of this intergenic region for Shh transcription in teeth. Furthermore, we clarified the binding of Lef1/Tcfs to the new enhancer and MRCS1, suggesting that Wnt/β-catenin signaling regulates Shh signaling in the oral cavity via these enhancers." {{SHH}}
 
|}
|}
{| class="wikitable mw-collapsible mw-collapsed"
{| class="wikitable mw-collapsible mw-collapsed"
Line 35: Line 44:
| [[File:Mark_Hill.jpg|90px|left]] {{Most_Recent_Refs}}
| [[File:Mark_Hill.jpg|90px|left]] {{Most_Recent_Refs}}


Search term: [http://www.ncbi.nlm.nih.gov/pubmed/?term=Tooth+Embryology ''Tooth Embryology'']
Search term: [http://www.ncbi.nlm.nih.gov/pubmed/?term=Tooth+Embryology ''Tooth Embryology''] | [http://www.ncbi.nlm.nih.gov/pubmed/?term=Tooth+Development ''Tooth Development''] | [http://www.ncbi.nlm.nih.gov/pubmed/?term=Odontoblast+Development ''Odontoblast Development''] | [http://www.ncbi.nlm.nih.gov/pubmed/?term=dentinogenesis dentinogenesis] | [http://www.ncbi.nlm.nih.gov/pubmed/?term=Ameloblast+Development ''Ameloblast Development''] | [http://www.ncbi.nlm.nih.gov/pubmed/?term=enamelogenesis enamelogenesis]
 
 
|}
{| class="wikitable mw-collapsible mw-collapsed"
! Older papers &nbsp;
|-
| {{Older papers}}
* Review - '''PAX9 gene mutations and tooth agenesis'''{{#pmid:28155232|PMID28155232}} "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'''{{#pmid:26755699|PMID26755699}} "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.'''{{#pmid:19576204|PMID19576204}} "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."


<pubmed limit=5>Tooth Embryology</pubmed>
* '''Expression survey of genes critical for tooth development in the human embryonic tooth germ.'''{{#pmid:17394220|PMID17394220}} "examined the expression patterns of several regulatory genes, including {{BMP}}4, {{FGF}}8, 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."
|}
|}
== Textbooks ==
== Textbooks ==
[[File:Rat-neonatal_teeth.jpg|thumb|Neonatal rat teeth]]
* '''Human Embryology '''(2nd ed.) Larson Chapter 14 p443-455  
* '''Human Embryology '''(2nd ed.) Larson Chapter 14 p443-455  
* '''The Developing Human: Clinically Oriented Embryology '''(6th ed.) Moore and Persaud Chapter 20: P513-529  
* '''The Developing Human: Clinically Oriented Embryology '''(6th ed.) Moore and Persaud Chapter 20: P513-529  
Line 49: Line 71:
==Movies==
==Movies==
{|
{|
| {{Mouse tooth movie 1}}
| width=530px|<html5media height="540" width="512">File:Mouse tooth movie 01.mp4</html5media>
| 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>
| 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.{{#pmid:27588418|PMID27588418}}


The tooth germ is from a developing molar and the lingual side is on the left.
The tooth germ is from a developing molar and the lingual side is on the left.
 
<br>
{{Mouse tooth movie 1}}


|}
|}
Line 60: Line 83:
* inductive influence of neural crest with overlying ectoderm  
* inductive influence of neural crest with overlying ectoderm  


===Odontoblasts===
<div id="Odontoblast Cells"></div>
* neural crest-derived mesenchymal cells
===Odontoblast Cells===
The {{Odontoblast}} cells (dentinoblasts) are a population of {{neural crest}}-derived mesenchymal cells.
* differentiate under the influence of the enamel epithelium
* differentiate under the influence of the enamel epithelium
* form predentin
* form predentin
* calcifies to form dentin
* calcifies to form dentin (protects the dental pulp)
===Ameloblasts===
 
* produce enamal
Dentin
* Collagen - collagen type I (about 90%) collagen type III and type V
* Proteoglycans - chondroitin sulphate (biglycan and decorin), heparan sulphate (entactin and perlecan), keratan sulphate, and dermatan sulphate
* Laminins - only at epithelial-mesenchymal junction
* Formation - before tooth eruption (primary dentin) rate of 4–8 μm/day, after tooth eruption (secondary dentin) rate of 0.5 μm/day.
 
 
Abnormalities - Dentinogenesis Imperfecta Type I, II and III, Dentin Dysplasia Type I and II,
Osteogenesis Imperfecta
 
 
<div id="Ameloblast Cells"></div>
===Ameloblast Cells===
The {{Ameloblast}} cells a population of {{ectoderm}}-derived oral epithelium cells that produce the tooth enamel.
* Molecular - {{BMP}} and {{FGF}}
* tooth growth occurs in ossifying jaws
* tooth growth occurs in ossifying jaws
* periodontal ligament holds tooth in bone socket
* periodontal ligament holds tooth in bone socket
===Epithelial Root Sheath===
The Epithelial Root Sheath or Hertwig's epithelial root sheath (HERS) these epithelial cells differentiate into cementoblasts through {{epithelial mesenchymal transition}} (EMT) and during the tooth root development also induce odontoblastic differentiation of the dental papilla through epithelial mesenchymal interaction (EMI). Recent research has identified a method to establish HERS cell lines.{{#pmid:30606270|PMID30606270}}


==Tooth Stages==
==Tooth Stages==
[[File:Tooth_development_stage.jpg|thumb|Tooth development stages<ref name="PMID19266065"><pubmed>19266065</pubmed>| [http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=2651620&tool=pmcentrez PMCID: PMC2651620]</ref>]]
[[File:Tooth_development_stage.jpg|thumb|Tooth development stages{{#pmid:19266065|PMID19266065}}]]


{{Tooth stages table01}}
{{Tooth stages table01}}
Line 80: Line 124:
==Human 2 Sets of Teeth==
==Human 2 Sets of Teeth==
[[File:Human permanent teeth.jpg|thumb|300px|Human permanent teeth appearance (eruption)]]
[[File:Human permanent teeth.jpg|thumb|300px|Human permanent teeth appearance (eruption)]]
===Human Dentition Timeline===
===Human Dentition Timeline===
<div id="Table Human Dentition"></div>
<div id="Table Human Dentition"></div>
{|
! 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: [[Book_-_Manual_of_Human_Embryology_17-2#The_Teeth|The Teeth (1912)]]<ref>[[Book_-_Manual_of_Human_Embryology_II|Manual of Human Embryology II]] Keibel, F. and [[Embryology_History_-_Franklin_Mall |Mall, F.P.]] J. B. Lippincott Company, Philadelphia (1912)</ref>
{{Tooth timeline table1}}
 
===Deciduous Teeth===
===Deciduous Teeth===
* 20 deciduous teeth
* 20 deciduous teeth
Line 147: Line 149:
local ectodermal thickening expresses several signaling molecules
local ectodermal thickening expresses several signaling molecules
these in turn signal to the underlying mesenchyme triggering mesenchymal condensation
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)
(epithelially expressed {{Bmp}}4 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.
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.
Mouse ({{ME11}} and {{ME12}}) - 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,
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.
{{Bmp}}2 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)
(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)
(More? [[Developmental Mechanism - Epithelial Mesenchymal Interaction|Epithelial Mesenchymal Interaction]])


==Periodontal Ligament==
==Periodontal Ligament==
Line 171: Line 173:


==Molecular Tooth Development==
==Molecular Tooth Development==
[[File:Tooth_molecular_development.jpg|thumb|Tooth molecular development<ref name="PMID19266065" />]]
[[File:Tooth_molecular_development.jpg|thumb|Tooth molecular development{{#pmid:19266065|PMID19266065}}]]
More than 300 genes have been associated with tooth development including: BMP4, FGF8, MSX1, MSX2, PAX9, PITX2, SHOX2, Delta/Notch, Hox-8, Runx2
More than 300 genes have been associated with tooth development including: BMP4, FGF8, MSX1, MSX2, PAX9, PITX2, SHOX2, Delta/Notch, Hox-8, Runx2


Line 193: Line 195:




'''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.<ref><pubmed>16651263</pubmed></ref>
'''{{BMP}}4''' 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.{{#pmid:16651263|PMID16651263}}
 
'''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.{{#pmid:26487719|PMID26487719}}


'''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.<ref name="PMID26487719"><pubmed>26487719</pubmed></ref>
'''Foxi3''' forkhead-box transcription factor inhibits formation of enamel knots and cervical loops and therefore the differentiation of dental epithelium.{{#pmid:26450968|PMID26450968}}


'''Foxi3''' forkhead-box transcription factor inhibits formation of enamel knots and cervical loops and therefore the differentiation of dental epithelium.<ref name="PMID26450968"><pubmed>26450968</pubmed></ref>
 
 
'''Hey1''' and '''Hey2''' basic helix-loop-helix type transcription factors are differently expressed during mouse tooth development{{#pmid:29155305|PMID29155305}} Hey family (also known as Chf, Herp, Hesr, and Hrt).
* Hey2 transcripts were restricted to the undifferentiated inner enamel epithelium and down-regulated in preameloblasts and ameloblasts.
* Hey1 expressed in pre-ameloblasts and down-regulated in differentiated ameloblasts.


==Abnormalities==
==Abnormalities==
[[File:Inherited_dentine_disorders.jpg|thumb|Inherited dentine disorders<ref><pubmed>19021896</pubmed></ref>]]
{|
|-bgcolor="FFCC00"
! colspan=2|{{ICD-11}} {{ICD11weblink}}1874269997 face, mouth or teeth]
|-bgcolor="FEF9E7"
|
{{ICD11weblink}}1431065078 LA30 Structural developmental anomalies of teeth and periodontal tissues]
 
* {{ICD11weblink}}413433873 LA30.0 Anodontia] - ''a genetic disorder commonly defined as the absence of all teeth, affecting both, temporary and permanent dentitions, and is extremely rarely encountered in a pure form without any associated abnormalities. Rare but more common than complete anodontia are hypodontia.''
* {{ICD11weblink}}30994440 LA30.1 Hypodontia] - ''a lack of one or a few (less than 6) permanent teeth, without any systemic disorders.'' 
* {{ICD11weblink}}1559717619 LA30.2 Oligodontia] - ge''netic condition characterized by the development of fewer than the normal number of teeth. The diagnosis of Oligodontia is usually made in cases in which more than six teeth are missing.''
* {{ICD11weblink}}2112834949 LA30.3 Hyperdontia] - ''condition of having supernumerary teeth, or teeth which appear in addition to the regular number of teeth.''
* {{ICD11weblink}}155327866 LA30.4 Abnormalities of size or form of teeth] -  tuberculum paramolare, Concrescence of teeth, Gemination of teeth, Enamel pearls, Talon for anterior teeth, Tuberculated premolar, Leong’s premolar, Evaginated odontoma for posterior teeth, Microdontia, Macrodontia, Fused mandibular incisors, Fusion of teeth, Taurodontism, Dens evaginatus, Dens in dente, Talon cusp, Abnormal cusps, Tapered teeth, Shovel teeth, Conical teeth, Globodontia
* {{ICD11weblink}}317316634LA30.5 Anomalies in tooth resorption or loss] 
* {{ICD11weblink}}1923123066 LA30.6 Amelogenesis imperfecta] - ''rare abnormal formation of the enamel or external layer of the crown of teeth. Amelogenesis imperfecta is due to the malfunction of the proteins in the enamel: ameloblastin, enamelin, tuftelin and amelogenin. People afflicted with amelogenesis imperfecta have teeth with abnormal color: yellow, brown or grey; this disorder can afflict any number of teeth of both dentitions. The teeth have a higher risk for dental cavities and are hypersensitive to temperature changes as well as rapid attrition, excessive calculus deposition, and gingival hyperplasia.'' 
* {{ICD11weblink}}1262020657 LA30.7 Dentine dysplasia]
* {{ICD11weblink}}2090257992 LA30.8 Dentinogenesis imperfecta]] 
* {{ICD11weblink}}1051464354 LA30.9 Odontogenesis imperfecta]
|}
[[File:Inherited_dentine_disorders.jpg|thumb|Inherited dentine disorders{{#pmid:19021896|PMID19021896}}]]
 
===Adontia===
===Adontia===
A total lack of tooth development.
A total lack of tooth development.
Line 234: Line 261:


(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.
(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]]  
:'''Links:''' [[Abnormal Development - Syphilis]]  
Line 247: Line 275:


===Reviews===
===Reviews===
<pubmed>24495023</pubmed>
{{#pmid:30473389}}
<pubmed>19875280</pubmed>
 
<pubmed>17209531</pubmed>
{{#pmid:28155232}}
<pubmed>16838332</pubmed>
 
<pubmed>16753804</pubmed>
{{#pmid:27131345}}
<pubmed>12615136</pubmed>
 
<pubmed>12640730</pubmed>
{{#pmid:24495023}}
 
{{#pmid:19875280}}
 
{{#pmid:17209531}}
 
{{#pmid:16838332}}
 
{{#pmid:16753804}}
 
{{#pmid:12615136}}
 
{{#pmid:12640730}}


===Articles===
===Articles===


<pubmed>17394220</pubmed>
{{#pmid:30683845}}
<pubmed>16632755</pubmed>
 
<pubmed>16651263</pubmed>
{{#pmid:17394220}}
<pubmed>9520113</pubmed>
 
{{#pmid:16632755}}
 
{{#pmid:16651263}}
 
{{#pmid:9520113}}


===Search PubMed===
===Search PubMed===
Line 271: Line 316:
==Additional Images==
==Additional Images==
[[:Category:Tooth]] | [[:Category:Integumentary]]
[[:Category:Tooth]] | [[:Category:Integumentary]]
<gallery>
<gallery>
File:Tooth_development_stage.jpg|Tooth development stage
File:Tooth_development_stage.jpg|Tooth development stage
Line 279: Line 325:
File:Rat-neonatal_teeth.jpg|Rat - neonatal teeth
File:Rat-neonatal_teeth.jpg|Rat - neonatal teeth
</gallery>
</gallery>
===Historic===
===Historic Images===
[[Book - Human Embryology and Morphology 5|Development and Morphology of the Teeth (1902)]]
{{Historic Disclaimer}}
 
{{Ref- Keith1902}} [[Book - Human Embryology and Morphology 5|Development and Morphology of the Teeth (1902)]]
 
<gallery>
<gallery>
File:Keith1902 fig047.jpg|Fig. 47. Showing the parts of an incisor tooth.
File:Keith1902 fig047.jpg|Fig. 47. Showing the parts of an incisor tooth.
Line 287: Line 336:
File:Keith1902 fig050.jpg|Fig. 50. A. The tritubercular Type of Tooth.
File:Keith1902 fig050.jpg|Fig. 50. A. The tritubercular Type of Tooth.
</gallery>
</gallery>
[[Book_-_Manual_of_Human_Embryology_17-2#The_Teeth|The Teeth (1912)]]
 
{{Ref-GrosserLewisMcMurrich1912}} [[Book_-_Manual_of_Human_Embryology_17-2#The_Teeth|The Teeth (1912)]]
<gallery>
<gallery>
File:Keibel_Mall_2_262.jpg|Fig. 262. Section through the dental ridge of the lower jaw of embryos.
File:Keibel_Mall_2_262.jpg|Fig. 262. Section through the dental ridge of the lower jaw of embryos.
Line 295: Line 345:
File:Keibel_Mall_2_table_teeth.jpg|Table - Dentition Timeline
File:Keibel_Mall_2_table_teeth.jpg|Table - Dentition Timeline
</gallery>
</gallery>
[[Book_-_Text-Book_of_Embryology_12#The_Teeth|The Teeth (1921)]]
 
{{Ref-Bailey1921}} [[Book_-_Text-Book_of_Embryology_12#The_Teeth|The Teeth (1921)]]
<gallery>
<gallery>
File:Bailey251.jpg|Fig. 252. Section of developing tooth from a 3 months human fetus.
File:Bailey251.jpg|Fig. 252. Section of developing tooth from a 3 months human fetus.
Line 303: Line 354:
File:Baileytable05.jpg|Permanent teeth
File:Baileytable05.jpg|Permanent teeth
</gallery>
</gallery>
==Terms==
==Terms==
 
{{Tooth terms}}


== External Links ==
== External Links ==

Latest revision as of 07:17, 2 January 2020

Embryology - 28 Mar 2024    Facebook link Pinterest link Twitter link  Expand to Translate  
Google Translate - select your language from the list shown below (this will open a new external page)

العربية | català | 中文 | 中國傳統的 | français | Deutsche | עִברִית | हिंदी | bahasa Indonesia | italiano | 日本語 | 한국어 | မြန်မာ | Pilipino | Polskie | português | ਪੰਜਾਬੀ ਦੇ | Română | русский | Español | Swahili | Svensk | ไทย | Türkçe | اردو | ייִדיש | Tiếng Việt    These external translations are automated and may not be accurate. (More? About Translations)

Introduction

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)


After placed formation, there are four key 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

Recent molecular animal model studies have shown that epithelial Wnt/β-catenin signaling is sufficient to initiate tooth development through activating Shh, Bmps, Fgfs and Wnts in the dental epithelium.[1] This then initiates the expression of odontogenic genes in the underlying mesenchyme.


Historic Embryology
Oscar Hertwig (1849-1922)

Oscar Hertwig (1849-1922) was a German embryologist and anatomist who first identified in amphibia tooth development, and was subsequently named Hertwig's epithelial root sheath (HERS). In amphibia, this is a permanent structure. In mammals, this is a transient structure, assembled during early tooth root formation and elongation. Later the HERS becomes fenestrated and reduced to the epithelial rests of Malassez (ERM).[2]


Links: gastrointestinal tract

Integumentary Links: integumentary | Lecture | hair | tooth | nail | integumentary gland | mammary gland | vernix caseosa | melanocyte | touch | Eyelid | outer ear | Histology | integumentary abnormalities | Category:Integumentary
Hair Links  
Hair Links: Overview | Lanugo | Neonatal | Vellus | Terminal | Hair Follicle | Follicle Phases | Stem Cells | Molecular | Pattern | Puberty | Histology | Hair Colour | Arrector Pili Muscle | Hair Loss | Integumentary
Touch Links  
Touch Links: Touch Receptors | Touch Pathway | Pacinian Corpuscle | Meissner's Corpuscle | Merkel Cell | Sensory Modalities | Neural Crest Development | Neural System Development | Student project | Integumentary | Sensory System
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
Tinycc  
http://tiny.cc/Integument_Development
Historic Tooth Development  
1902 Tooth Development | 1912 The Teeth | 1921 The Teeth

Some Recent Findings

Tooth eruption signaling[3]
  • Immortalized Hertwig's epithelial root sheath cell line works as model for epithelial-mesenchymal interaction during tooth root formation[4] "Hertwig's epithelial root sheath (HERS) is critical for epithelial-mesenchymal interaction (EMI) during tooth root formation. However, the exact roles of HERS in odontogenic differentiation by EMI have not been well characterized, because primary HERS cells are difficult to obtain. Immortalized cell lines constitute crucial scientific tools, while there are few HERS cell lines available. Our previous study has successfully established immortalized HERS cell lines. Here, we confirmed the phenotype of our HERS-H1 by verifying its characteristics and functions in odontogenic differentiation through EMI. The HERS-H1-conditioned medium (CM-H1) effectively enhanced odontogenic differentiation of dental papilla cells (DPCs) in vitro. Furthermore, Smad4 and p-Smad1/5/8 were significantly activated in DPCs treated with CM-H1, and this activation was attenuated by noggin. In vivo, our implanted recombinants of HERS-H1 and DPCs exhibited mineralized tissue formation and expression of Smad4, p-Smad1/5/8, and odontogenic differentiation markers. Our results indicated that HERS-H1 promoted DPCs odontoblastic differentiation via bone morphogenetic protein/Smad signaling. HERS-H1 exhibits relevant key molecular characteristics and constitutes a new biological model for basic research on HERS and the dental EMI during root development and regeneration."
  • Parathyroid hormone-related peptide (1-34) promotes tooth eruption and inhibits osteogenesis of dental follicle cells during tooth development[5] "Dental follicle cells (DFCs) activate and recruit osteoclasts for tooth development and tooth eruption, whereas DFCs themselves differentiate into osteoblasts to form alveolar bone surrounding tooth roots through the interaction with Hertwig's epithelial root sheath (HERS). Also during tooth development, parathyroid hormone-related peptide (PTHrP) is expressed surrounding the tooth germ. Thus, we aimed to investigate the effect of PTHrP (1-34) on bone resorption and osteogenesis of DFCs in vitro and in vivo. In vitro studies demonstrated that DFCs cocultured with HERS cells expressed higher levels of BSP and OPN than the DFCs control group, whereas cocultured DFCs treated with PTHrP (1-34) had lower expressions of ALP, RUNX2, BSP, and OPN than the cocultured DFCs control group. Moreover, we found PTHrP (1-34) inhibited osteogenesis of cocultured DFCs by inactivating the Wnt/β-catenin pathway. PTHrP (1-34) also increased the expression of RANKL/OPG ratio in DFCs. Consistently, in vivo study found that PTHrP (1-34) accelerated tooth eruption and inhibited alveolar bone formation. Therefore, these results suggest that PTHrP (1-34) accelerates tooth eruption and inhibits osteogenesis of DFCs by inactivating Wnt/β-catenin pathway."
  • Autocrine regulation of mesenchymal progenitor cell fates orchestrates tooth eruption[6] "Formation of functional skeletal tissues requires highly organized steps of mesenchymal progenitor cell differentiation. The dental follicle (DF) surrounding the developing tooth harbors mesenchymal progenitor cells for various differentiated cells constituting the tooth root–bone interface and coordinates tooth eruption in a manner dependent on signaling by parathyroid hormone-related peptide (PTHrP) and the PTH/PTHrP receptor (PPR). However, the identity of mesenchymal progenitor cells in the DF and how they are regulated by PTHrP-PPR signaling remain unknown. Here, we show that the PTHrP-PPR autocrine signal maintains physiological cell fates of DF mesenchymal progenitor cells to establish the functional periodontal attachment apparatus and orchestrates tooth eruption. A single-cell RNA-seq analysis revealed cellular heterogeneity of PTHrP+ cells, wherein PTHrP+ DF subpopulations abundantly express PPR. Cell lineage analysis using tamoxifen-inducible PTHrP-creER mice revealed that PTHrP+ DF cells differentiate into cementoblasts on the acellular cementum, periodontal ligament cells, and alveolar cryptal bone osteoblasts during tooth root formation. PPR deficiency induced a cell fate shift of PTHrP+ DF mesenchymal progenitor cells to nonphysiological cementoblast-like cells precociously forming the cellular cementum on the root surface associated with up-regulation of Mef2c and matrix proteins, resulting in loss of the proper periodontal attachment apparatus and primary failure of tooth eruption, closely resembling human genetic conditions caused by PPR mutations."
  • Persistent Wnt/β-catenin signaling in mouse epithelium induces the ectopic Dspp expression in cheek mesenchyme[1] "Tooth development is accomplished by a series of epithelial-mesenchyme interactions. Epithelial Wnt/β-catenin signaling is sufficient to initiate tooth development by activating Shh, Bmps, Fgfs and Wnts in dental epithelium, which in turn, triggered the expression of odontogenic genes in the underlying mesenchyme. Although constitutive activation of Wnt/β-catenin signaling in oral ectoderm resulted in the continuous tooth formation throughout the life span, if the epithelial Wnt/β-catenin signaling could induce the mesenchyme other than oral mesenchyme still required to be elucidated. In this study, we found that in the K14-cre; Ctnnb1ex3f mice, the markers of dental epithelium, such as Pitx2, Shh, Bmp2, Fgf4, and Fgf8, were not only activated in the oral ectoderm, but also in the cheek epithelium. Surprisingly, the underlying cheek mesenchymal cells were elongated and expressed Dspp. Further investigations detected that the expression of Msx1 and Runx2 extended from oral to cheek mesenchyme. These findings suggested that epithelial Wnt/β-catenin signaling was capable of inducing Dspp expression in non-dental mesenchyme. ...In summary, our findings suggested that the epithelial Wnt/β-catenin signaling could induce craniofacial mesenchyme into odontogenic program and promote odontoblast differentiation.
  • Upstream Enhancer Elements of Shh Regulate Oral and Dental Patterning[7] "Sonic hedgehog ( Shh) is important in pattern formation during development. Shh transcription is modulated by a long-range regulatory mechanism containing a number of enhancers, which are spread over nearly 850 kb in the mouse genome. Shh enhancers in the nervous system have been found between intron and 430 kb upstream of Shh. Enhancers in the oral cavity, pharynx, lung, gut, and limbs have been discovered between 610 kb and 850 kb upstream of Shh. However, the intergenic region ranging from 430 to 610 kb upstream of Shh remains to be elucidated. In the present study, we found a novel long-range enhancer located 558 kb upstream of Shh. The enhancer showed in vivo activity in oral cavity and whiskers. A targeted deletion from the novel enhancer to mammal reptile conserved sequence 1 (MRCS1), which is a known enhancer of Shh in oral cavity, resulted in supernumerary molar formation, confirming the essential role of this intergenic region for Shh transcription in teeth. Furthermore, we clarified the binding of Lef1/Tcfs to the new enhancer and MRCS1, suggesting that Wnt/β-catenin signaling regulates Shh signaling in the oral cavity via these enhancers." SHH
More recent papers  
Mark Hill.jpg
PubMed logo.gif

This table allows an automated computer search of the external PubMed database using the listed "Search term" text link.

  • This search now requires a manual link as the original PubMed extension has been disabled.
  • The displayed list of references do not reflect any editorial selection of material based on content or relevance.
  • References also appear on this list based upon the date of the actual page viewing.


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.

More? References | Discussion Page | Journal Searches | 2019 References | 2020 References

Search term: Tooth Embryology | Tooth Development | Odontoblast Development | dentinogenesis | Ameloblast Development | enamelogenesis


Older papers  
These papers originally appeared in the Some Recent Findings table, but as that list grew in length have now been shuffled down to this collapsible table.

See also the Discussion Page for other references listed by year and References on this current page.

  • Review - PAX9 gene mutations and tooth agenesis[8] "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[9] "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.[10] "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.[11] "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."

Textbooks

Neonatal rat teeth
  • 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

Movies

<html5media height="540" width="512">File:Mouse tooth movie 01.mp4</html5media> 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.[12]

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

Mouse-tooth-icon.jpg
 ‎‎Tooth E12.5-17
Page | Play

Development Overview

  • ectoderm, mesoderm and neural crest ectomesenchyme contribute
  • inductive influence of neural crest with overlying ectoderm

Odontoblast Cells

The odontoblast cells (dentinoblasts) are a population of neural crest-derived mesenchymal cells.

  • differentiate under the influence of the enamel epithelium
  • form predentin
  • calcifies to form dentin (protects the dental pulp)

Dentin

  • Collagen - collagen type I (about 90%) collagen type III and type V
  • Proteoglycans - chondroitin sulphate (biglycan and decorin), heparan sulphate (entactin and perlecan), keratan sulphate, and dermatan sulphate
  • Laminins - only at epithelial-mesenchymal junction
  • Formation - before tooth eruption (primary dentin) rate of 4–8 μm/day, after tooth eruption (secondary dentin) rate of 0.5 μm/day.


Abnormalities - Dentinogenesis Imperfecta Type I, II and III, Dentin Dysplasia Type I and II, Osteogenesis Imperfecta


Ameloblast Cells

The ameloblast cells a population of ectoderm-derived oral epithelium cells that produce the tooth enamel.

  • Molecular - BMP and FGF
  • tooth growth occurs in ossifying jaws
  • periodontal ligament holds tooth in bone socket


Epithelial Root Sheath

The Epithelial Root Sheath or Hertwig's epithelial root sheath (HERS) these epithelial cells differentiate into cementoblasts through epithelial mesenchymal transition (EMT) and during the tooth root development also induce odontoblastic differentiation of the dental papilla through epithelial mesenchymal interaction (EMI). Recent research has identified a method to establish HERS cell lines.[13]


Tooth Stages

Tooth development stages[14]
Stage
Image
Human
(weeks)
Mouse
(days)
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  
Stage
Image
Human
(weeks)
Mouse
(days)
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

Human Dentition Timeline
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
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
Approximate timings only, vary considerably according to racial, climatic, and nutritive conditions.
Data source: Keibel and Mall (1912)[15] The teeth

    Links: tooth

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 and E12) - 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? 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[14]

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)

Delta/Notch

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.[16]

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.[17]

Foxi3 forkhead-box transcription factor inhibits formation of enamel knots and cervical loops and therefore the differentiation of dental epithelium.[18]


Hey1 and Hey2 basic helix-loop-helix type transcription factors are differently expressed during mouse tooth development[19] Hey family (also known as Chf, Herp, Hesr, and Hrt).

  • Hey2 transcripts were restricted to the undifferentiated inner enamel epithelium and down-regulated in preameloblasts and ameloblasts.
  • Hey1 expressed in pre-ameloblasts and down-regulated in differentiated ameloblasts.

Abnormalities

 ICD-11 face, mouth or teeth

LA30 Structural developmental anomalies of teeth and periodontal tissues

  • LA30.0 Anodontia - a genetic disorder commonly defined as the absence of all teeth, affecting both, temporary and permanent dentitions, and is extremely rarely encountered in a pure form without any associated abnormalities. Rare but more common than complete anodontia are hypodontia.
  • LA30.1 Hypodontia - a lack of one or a few (less than 6) permanent teeth, without any systemic disorders.
  • LA30.2 Oligodontia - genetic condition characterized by the development of fewer than the normal number of teeth. The diagnosis of Oligodontia is usually made in cases in which more than six teeth are missing.
  • LA30.3 Hyperdontia - condition of having supernumerary teeth, or teeth which appear in addition to the regular number of teeth.
  • LA30.4 Abnormalities of size or form of teeth - tuberculum paramolare, Concrescence of teeth, Gemination of teeth, Enamel pearls, Talon for anterior teeth, Tuberculated premolar, Leong’s premolar, Evaginated odontoma for posterior teeth, Microdontia, Macrodontia, Fused mandibular incisors, Fusion of teeth, Taurodontism, Dens evaginatus, Dens in dente, Talon cusp, Abnormal cusps, Tapered teeth, Shovel teeth, Conical teeth, Globodontia
  • Anomalies in tooth resorption or loss
  • LA30.6 Amelogenesis imperfecta - rare abnormal formation of the enamel or external layer of the crown of teeth. Amelogenesis imperfecta is due to the malfunction of the proteins in the enamel: ameloblastin, enamelin, tuftelin and amelogenin. People afflicted with amelogenesis imperfecta have teeth with abnormal color: yellow, brown or grey; this disorder can afflict any number of teeth of both dentitions. The teeth have a higher risk for dental cavities and are hypersensitive to temperature changes as well as rapid attrition, excessive calculus deposition, and gingival hyperplasia.
  • LA30.7 Dentine dysplasia
  • LA30.8 Dentinogenesis imperfecta]
  • LA30.9 Odontogenesis imperfecta
Inherited dentine disorders[20]

Adontia

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.

Hypodontia

Lack of development of one or more teeth.

Hypohidrotic Ectodermal Dysplasia

Maldevelopment of one or more ectodermal-derived tissues.

Microdontia

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

References

  1. 1.0 1.1 Zhou N, Li N, Liu J, Wang Y, Gao J, Wu Y, Chen X, Liu C & Xiao J. (2018). Persistent Wnt/β-catenin signaling in mouse epithelium induces the ectopic Dspp expression in cheek mesenchyme. Organogenesis , , 1-12. PMID: 30570432 DOI.
  2. Luan X, Ito Y & Diekwisch TG. (2006). Evolution and development of Hertwig's epithelial root sheath. Dev. Dyn. , 235, 1167-80. PMID: 16450392 DOI.
  3. Richman JM. (2019). Shedding new light on the mysteries of tooth eruption. Proc. Natl. Acad. Sci. U.S.A. , 116, 353-355. PMID: 30602459 DOI.
  4. Zhang S, Li X, Wang S, Yang Y, Guo W, Chen G & Tian W. (2020). Immortalized Hertwig's epithelial root sheath cell line works as model for epithelial-mesenchymal interaction during tooth root formation. J. Cell. Physiol. , 235, 2698-2709. PMID: 31512758 DOI.
  5. Zhang J, Liao L, Li Y, Xu Y, Guo W, Tian W & Zou S. (2019). Parathyroid hormone-related peptide (1-34) promotes tooth eruption and inhibits osteogenesis of dental follicle cells during tooth development. J. Cell. Physiol. , 234, 11900-11911. PMID: 30584670 DOI.
  6. Takahashi A, Nagata M, Gupta A, Matsushita Y, Yamaguchi T, Mizuhashi K, Maki K, Ruellas AC, Cevidanes LS, Kronenberg HM, Ono N & Ono W. (2019). Autocrine regulation of mesenchymal progenitor cell fates orchestrates tooth eruption. Proc. Natl. Acad. Sci. U.S.A. , 116, 575-580. PMID: 30509999 DOI.
  7. Seo H, Amano T, Seki R, Sagai T, Kim J, Cho SW & Shiroishi T. (2018). Upstream Enhancer Elements of Shh Regulate Oral and Dental Patterning. J. Dent. Res. , , 22034518758642. PMID: 29481312 DOI.
  8. Bonczek O, Balcar VJ & Šerý O. (2017). PAX9 gene mutations and tooth agenesis: A review. Clin. Genet. , 92, 467-476. PMID: 28155232 DOI.
  9. Li J, Chatzeli L, Panousopoulou E, Tucker AS & Green JB. (2016). Epithelial stratification and placode invagination are separable functions in early morphogenesis of the molar tooth. Development , 143, 670-81. PMID: 26755699 DOI.
  10. Huang X, Bringas P, Slavkin HC & Chai Y. (2009). Fate of HERS during tooth root development. Dev. Biol. , 334, 22-30. PMID: 19576204 DOI.
  11. Lin D, Huang Y, He F, Gu S, Zhang G, Chen Y & Zhang Y. (2007). Expression survey of genes critical for tooth development in the human embryonic tooth germ. Dev. Dyn. , 236, 1307-12. PMID: 17394220 DOI.
  12. Morita R, Kihira M, Nakatsu Y, Nomoto Y, Ogawa M, Ohashi K, Mizuno K, Tachikawa T, Ishimoto Y, Morishita Y & Tsuji T. (2016). Coordination of Cellular Dynamics Contributes to Tooth Epithelium Deformations. PLoS ONE , 11, e0161336. PMID: 27588418 DOI.
  13. Li X, Zhang S, Zhang Z, Guo W, Chen G & Tian W. (2019). Development of immortalized Hertwig's epithelial root sheath cell lines for cementum and dentin regeneration. Stem Cell Res Ther , 10, 3. PMID: 30606270 DOI.
  14. 14.0 14.1 Koussoulakou DS, Margaritis LH & Koussoulakos SL. (2009). A curriculum vitae of teeth: evolution, generation, regeneration. Int. J. Biol. Sci. , 5, 226-43. PMID: 19266065
  15. Grosser O. Lewis FT. and McMurrich JP. The Development of the Digestive Tract and of the Organs of Respiration. (1912) chapter 17, vol. 2, in Keibel F. and Mall FP. Manual of Human Embryology II. (1912) J. B. Lippincott Company, Philadelphia.
  16. Ogawa T, Kapadia H, Feng JQ, Raghow R, Peters H & D'Souza RN. (2006). Functional consequences of interactions between Pax9 and Msx1 genes in normal and abnormal tooth development. J. Biol. Chem. , 281, 18363-9. PMID: 16651263 DOI.
  17. Meng T, Huang Y, Wang S, Zhang H, Dechow PC, Wang X, Qin C, Shi B, D'Souza RN & Lu Y. (2015). Twist1 Is Essential for Tooth Morphogenesis and Odontoblast Differentiation. J. Biol. Chem. , 290, 29593-602. PMID: 26487719 DOI.
  18. Jussila M, Aalto AJ, Sanz Navarro M, Shirokova V, Balic A, Kallonen A, Ohyama T, Groves AK, Mikkola ML & Thesleff I. (2015). Suppression of epithelial differentiation by Foxi3 is essential for molar crown patterning. Development , 142, 3954-63. PMID: 26450968 DOI.
  19. Kibe K, Nakatomi M, Kataoka S, Toyono T & Seta Y. (2018). Hey1 and Hey2 are differently expressed during mouse tooth development. Gene Expr. Patterns , 27, 99-105. PMID: 29155305 DOI.
  20. Barron MJ, McDonnell ST, Mackie I & Dixon MJ. (2008). Hereditary dentine disorders: dentinogenesis imperfecta and dentine dysplasia. Orphanet J Rare Dis , 3, 31. PMID: 19021896 DOI.


Journals

Reviews

Chang B, Svoboda KKH & Liu X. (2019). Cell polarization: From epithelial cells to odontoblasts. Eur. J. Cell Biol. , 98, 1-11. PMID: 30473389 DOI.

Bonczek O, Balcar VJ & Šerý O. (2017). PAX9 gene mutations and tooth agenesis: A review. Clin. Genet. , 92, 467-476. PMID: 28155232 DOI.

Kawashima N & Okiji T. (2016). Odontoblasts: Specialized hard-tissue-forming cells in the dentin-pulp complex. Congenit Anom (Kyoto) , 56, 144-53. PMID: 27131345 DOI.

Peterkova R, Hovorakova M, Peterka M & Lesot H. (2014). Three-dimensional analysis of the early development of the dentition. Aust Dent J , 59 Suppl 1, 55-80. PMID: 24495023 DOI.

Bei M. (2009). Molecular genetics of tooth development. Curr. Opin. Genet. Dev. , 19, 504-10. PMID: 19875280 DOI.

Seppala M, Zoupa M, Onyekwelu O & Cobourne MT. (2006). Tooth development: 1. Generating teeth in the embryo. Dent Update , 33, 582-4, 586-8, 590-1. PMID: 17209531

Thesleff I. (2006). The genetic basis of tooth development and dental defects. Am. J. Med. Genet. A , 140, 2530-5. PMID: 16838332 DOI.

Tompkins K. (2006). Molecular mechanisms of cytodifferentiation in mammalian tooth development. Connect. Tissue Res. , 47, 111-8. PMID: 16753804 DOI.

Cobourne MT & Sharpe PT. (2003). Tooth and jaw: molecular mechanisms of patterning in the first branchial arch. Arch. Oral Biol. , 48, 1-14. PMID: 12615136

Sharpe PT. (2001). Neural crest and tooth morphogenesis. Adv. Dent. Res. , 15, 4-7. PMID: 12640730 DOI.

Articles

Yuan X, Cao X & Yang S. (2019). IFT80 is required for stem cell proliferation, differentiation, and odontoblast polarization during tooth development. Cell Death Dis , 10, 63. PMID: 30683845 DOI.

Lin D, Huang Y, He F, Gu S, Zhang G, Chen Y & Zhang Y. (2007). Expression survey of genes critical for tooth development in the human embryonic tooth germ. Dev. Dyn. , 236, 1307-12. PMID: 17394220 DOI.

Nakatomi M, Morita I, Eto K & Ota MS. (2006). Sonic hedgehog signaling is important in tooth root development. J. Dent. Res. , 85, 427-31. PMID: 16632755 DOI.

Ogawa T, Kapadia H, Feng JQ, Raghow R, Peters H & D'Souza RN. (2006). Functional consequences of interactions between Pax9 and Msx1 genes in normal and abnormal tooth development. J. Biol. Chem. , 281, 18363-9. PMID: 16651263 DOI.

Kettunen P & Thesleff I. (1998). Expression and function of FGFs-4, -8, and -9 suggest functional redundancy and repetitive use as epithelial signals during tooth morphogenesis. Dev. Dyn. , 211, 256-68. PMID: 9520113 <256::AID-AJA7>3.0.CO;2-G DOI.

Search PubMed

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

Additional Images

Category:Tooth | Category:Integumentary

Historic Images

Historic Disclaimer - information about historic embryology pages 
Mark Hill.jpg
Pages where the terms "Historic" (textbooks, papers, people, recommendations) appear on this site, and sections within pages where this disclaimer appears, indicate that the content and scientific understanding are specific to the time of publication. This means that while some scientific descriptions are still accurate, the terminology and interpretation of the developmental mechanisms reflect the understanding at the time of original publication and those of the preceding periods, these terms, interpretations and recommendations may not reflect our current scientific understanding.     (More? Embryology History | Historic Embryology Papers)

Template:Ref- Keith1902 Development and Morphology of the Teeth (1902)

Grosser O. Lewis FT. and McMurrich JP. The Development of the Digestive Tract and of the Organs of Respiration. (1912) chapter 17, vol. 2, in Keibel F. and Mall FP. Manual of Human Embryology II. (1912) J. B. Lippincott Company, Philadelphia. The Teeth (1912)

Bailey FR. and Miller AM. Text-Book of Embryology (1921) New York: William Wood and Co. The Teeth (1921)


Terms

Tooth Terms  
Tooth Development
  • ameloblast - population of ectoderm-derived oral epithelium cells that produce the tooth enamel.
  • cementoblast - follicular cells around tooth root that form cementum covering the tooth root.
  • dental papilla -
  • Hertwig's epithelial root sheath - (HERS) cells differentiate into cementoblasts through epithelial mesenchymal transition (EMT) and also induce odontoblastic differentiation of dental papilla through epithelial-mesenchymal interaction (EMI) during the tooth root development.
  • odontoblast - (dentinoblasts) are a population of neural crest-derived mesenchymal cells that produce predentin, that calcifies to form dentin (protects the dental pulp).
  • periodontal ligament - ligament that holds the tooth in the bone socket of the jaw.
  • sonic hedgehog - (SHH, Shh) a secreted growth factor sonic hedgehog that binds the patched (ptc) receptor on cell membrane.
Other Terms Lists  
Terms Lists: ART | Birth | Bone | Cardiovascular | Cell Division | Endocrine | Gastrointestinal | Genital | Genetic | Head | Hearing | Heart | Immune | Integumentary | Neonatal | Neural | Oocyte | Palate | Placenta | Radiation | Renal | Respiratory | Spermatozoa | Statistics | Tooth | Ultrasound | Vision | Historic | Drugs | Glossary

External Links

External Links Notice - The dynamic nature of the internet may mean that some of these listed links may no longer function. If the link no longer works search the web with the link text or name. Links to any external commercial sites are provided for information purposes only and should never be considered an endorsement. UNSW Embryology is provided as an educational resource with no clinical information or commercial affiliation.



Glossary Links

Glossary: A | B | C | D | E | F | G | H | I | J | K | L | M | N | O | P | Q | R | S | T | U | V | W | X | Y | Z | Numbers | Symbols | Term Link



Cite this page: Hill, M.A. (2024, March 28) Embryology Integumentary System - Tooth Development. Retrieved from https://embryology.med.unsw.edu.au/embryology/index.php/Integumentary_System_-_Tooth_Development

What Links Here?
© Dr Mark Hill 2024, UNSW Embryology ISBN: 978 0 7334 2609 4 - UNSW CRICOS Provider Code No. 00098G