Tooth Development Flashcards
What is the basic repeating structure of hydroxyapatite?
OH- ion surrounded by 3 Ca2+ ions, surrounded by 3 PO43- ions, enclosed by 6 Ca2+ ions
What is the result of F- substituting OH- in hydroxyapatite?
- stabilises the lattice
- makes it more acid resistant
- F- and prevention
What is the critical pH of hydroxyapatite and fluorapatite?
Hydroxyapatite: 5.5
Fluorapatite: 4.5
what are the three theories of mineralisation?
- Alkaline phosphotase hypothesis
- Nucleation ( homogeneous and heterogeneous)
- Matrix vesicles
What is the alkaline phosphatase hypothesis of mineralisation?
Alkaline phosphatase, an enzyme present in developing teeth and bones, drives the formation of apatite.
What is the homogeneous nucleation theory of mineralisation?
The formation of a 1st solid from a solution of ions in which no solid previously existed
Can homogeneous nucleation occur for hydroxyapatite?
No, hydroxyapatite crystals do not form spontaneously in a supersaturated solution
what is heterogenous nucleation?
A foreign solid will assist nucleation of a crystal
What may act as an epitactic agent in heterogeneous nucleation, promoting formation of crystals?
Organic matrix
what are possible nucleators of heterogenous nucleation?
Collagen
Proteoglycans
Lipids
Phosphoproteins
Where do crystals form in collagen structures?
In the gaps
what are the accepted theories of mineralisation?
- heterogeneous nucleation
- matrix vesicles
What is the first central tissue to form?
Dentine
What are matrix vesicles?
Membrane packages produced by cells, that contain high concentrations of Ca2+ and PO43- ions
What is the main benefit of matrix vesicles in mineralisation?
They provide an ideal micro environment for crystal formation and growth (mineralisation)
What is the function of matrix vesicles?
They help to initiate mineralisation in a tissue
What is the sequence of hard tissue mineralisation for a tooth?
- Dentine
- Enamel
- Cementum
Matrix vesicles are involved in the formation of what hard tissue?
Mantle dentine
What type of cells is dentine derived from?
Ectomesenchymal cells
What are the 4 stages of a tooth germ?
- Bud stage
- Cap stage
- Bell stage
- Crown stage
In what stage of tooth germ do hard tissues start to appear?
End of bell stage, start of crown stage
what cells form dentine?
Odontoblasts
Where are odontoblasts derived from?
From the cells of the dental papilla
At what part of the developing tooth does dentine formation begin?
At the cusp tip
What are the three stages of dentine formation?
- cytodifferentiation
- matrix formation
- mineralisation
what happens during the cytodifferentiation stage of dentine formation?
Cells change from papilla cells to odontoblasts. This requires instruction from epithelial cells.
what happens during the matrix formation stage of dentine formation?
Odontoblasts produce matrix and promote mineralisation
What type of cells are found in the enamel organ, and what does it form?
Cell type: epithelial cells
Forms: enamel
What type of cells are found in the dental papilla, and what does it form?
Cell type: ectomesenchymal cells
Forms: odontoblasts
What type of cells are found in the dental follicle, and what does it form?
Cell type: ectomesenchymal cells
Forms: supporting tissues ( PDL, bone, socket and cementum)
what are the five components of the enamel organ?
- Outer enamel epithelium
- Stellate reticulum
- Stratum intermedium
- Inner enamel epithelium
- Cervical loop
Give the 6 steps involved in the formation of dentine from the dental papilla
- Dental papilla cells divide
- Cells enlarge and cross acellular space
- Increased synthetic/ secretory organelles
- The organic matrix is secreted = predentine
- Odontoblasts retreat secreting predentine
- Predentine mineralises forming dentine
What process signals the start of enamel formation?
Disintegration of the basal lamina
What are the two initial types of dentine?
- Mantle dentine
- Circumpulpal dentine
What is the first formed dentine?
Mantle dentine
What is the mantle dentine characterised by?
- large collagen fibrils at 90 degrees to the ADJ
- matrix vesicles are involved in it’s formation
What will the inner enamel epithelium cells mature into?
Ameloblasts
what happens to epithelial cells as they mature?
They elongate
What direction do ameloblast’s move during enamel formation?
Upwards and outwards
What process has allowed for enamel prisms to crucially exist?
Tomes process
What governs the shape of enamel prisms?
- tomes process
- direction of retreat of ameloblasts
What is the final cue for onset of amelogenesis?
- Dentine formation
- Breakdown of basal lamina
What is the enamel organic matrix made up of?
Amorphous gel containing enamel proteins and enzymes
What are the three enamel proteins within the amorphous gel organic matrix?
- amelogenins (90%)
- enamelins (2%)
- tuftelin (confined to ADJ)
what are amelogenins rich in?
Proline and glutamine
What two features characterise amelogenins?
- hydrophobic
- thixotropic (changes in properties depending on conditions)
What are the three main roles of enamel proteins?
- aid nucleation of hydroxyapatite
- orientate and stabilise crystal growth
- broken down and lost during maturation
What does enamel require to mature?
Mineral ions to move IN and enamel matrix to move OUT
What proteins are contained in the enamel matrix that flows out?
Amelogenins
What proteins are contained in the enamel matrix that remains once mineral ions start to flow into enamel?
Enamelin
when is the tomes process lost?
When most of the enamel thickness is laid down
Why is the last formed enamel aprismatic?
Because there is no Tomes process present, it is lost once most of enamel thickness is laid down.
What is the protein layer, formed when maturation of enamel is complete and is the final ameloblast secretion, called?
Enamel cuticle or reduced enamel epithelium
When does the ‘reduced enamel epithelium’ form?
When enamel formation is complete
What are the three functions of reduced enamel epithelium?
- Protection of enamel surface from resorption or prevention of cementum formation
- Provide an epithelial lined pathway for eruption
- Forms initial junctional epithelium
Define:
The differentiation of cells into specialised tissues and organs during growth
Histogenesis
Define:
First stage of tooth development
Initiation stage
what is the vestibular lamina?
Contributes to the vestibule of the mouth, delineating the lips and cheeks from the teeth. Involved in formation of sulcus.
Define:
The second stage of tooth germ development
Bud stage
Define:
The third stage of tooth germ development
Cap stage
Define:
The fourth stage of tooth germ development
Bell stage
Define:
The last stage of tooth germ development
Crown stage or late bell stage
Define:
Outer layer of cuboidal cells that limits the enamel organ
External enamel epithelium
Define:
Two or three layers of cells sitting above the inner enamel epithelium
Stratum intermedium
Define:
A group of star-shaped cells located in the centre of the enamel organ
Stellate reticulum
Define:
Columnar shaped cells rich in RNA, connected by desmosomes to each other. Part of the enamel organ.
Inner enamel epithelium
Define:
A form of mesenchyme, in the embryo, consisting of neural crest cells and forms he tissues of the neck and cranium.
Ectomesenchyme
What growth factor does ectomesenchyme have receptors for which allows its condensation to occur?
FGF8
What does the primary epithelial band give rise to?
- dental lamina
- vestibular lamina
What process does the vestibular lamina undergo to form the vestibule between teeth and lips/cheeks?
Apoptosis
What week in tooth development does differentiation between dental and vestibular lamina occur?
Week 7
What week in tooth development does apoptosis of the vestibular lamina begin?
Week 9
What week in tooth development is apoptosis of vestibular lamina complete, leaving a sulcus ?
Week 12
what are the three overlapping phases of tooth development?
- Initiation
- Morphogenesis
- Histogenesis
What does epithelium (ectoderm) give rise to?
- enamel
- hyaline layer of root
what does mesenchyme (ectomesenchyme) give rise to?
- dentine
- pulp
- cementum
- periodontium
which tissue is thought to have odontogenic potential so initiates tooth development?
Epithelium
what are the three components of a tooth germ?
- enamel organ
- dental papilla
- dental follicle
What stage of tooth development is described here?:
- spherical/ovoid epithelial condensation
- cell proliferation
- no histodifferentiation or morphogenesis
Bud stage
What stage of tooth development is described here?:
- enamel organ formation
- histodifferentiation and morphogenesis
Bell stage
What stage of tooth development is described here?:
- cap shaped enamel organ
- little morphogenesis
- poorly histodifferentiatied
Cap stage
what is the role of inner enamel epithelium?
Forms ameloblasts which from enamel
what is the role of the stratum intermedium?
Synthesis and transport to and from the inner enamel epithelium
what is the role of the Stellate reticulum?
Maintenance of shape and protection
what is the role of outer enamel epithelium?
Maintenance of shape and exchange
What are the three transitory (temporary) structures of a developing tooth germ?
- Enamel knot
- Enamel niche
- Enamel septum
which transitory structure aids change in shape from cap to bell stage?
Enamel septum
Give examples of important genes involved in the initiation stage of tooth development
- Bmp2
- EGF
- MSX1
- msx2
-Shh
why does the basement membrane have to be intact in a developing tooth?
So that differentiation of mesenchyme to odontoblast can occur
What week of tooth development is initiation stage?
Week 6/7
What week of tooth development is bud stage?
Week 8
What week of tooth development is cap stage?
Week 9/10
What week of tooth development is bell stage?
Week 11/12
In bell and crown stages, when dental papilla cells signal to IEE cells, what happens to the IEE cells?
They elongate and polarise
What happens to the cervical loop during bell and crown stages?
Cells divide
During bell and crown stage, which cells invade acellular zone ( what will become the dental pulp in the long term)?
Mature Dental papilla cells
what do dental papilla cells mature into?
Odontoblasts
What do inner enamel epithelial cells develop into?
Ameloblasts
Where OEE cells and IEE cells meet, what is this called?
Cervical loop
What, in the long-term, is the cervical loop responsible for?
Root development
How does the odontoblast process form?
Pre-odontoblasts start to differentiate upon signalling from the ameloblasts, synthetic organelles are made and the nucleus retreats basally.
what happens to the basement membrane as odontoblast process forms?
It breaks down and is replaced by predentine
What are the stages of life for an ameloblast?
- Pre-secretory
- Secretory
- Transition
- Maturation
- Postmaturation
What stage of an ameloblast’s life is described:
Undergoes cytodifferentiation, morphodifferentiation, resorption of basal lamina and epithelial-mesenchymal interactions
Pre-secretory
What stage of an ameloblast’s life is described:
Ameloblasts shorten and 50% die
Transition
What stage of an ameloblast’s life is described:
Final degradation and withdrawal of matrix
Maturation
What stage of an ameloblast’s life is described:
Initial layer of aprismatic enamel formed, tomes process develops, matrix secretion to final thickness and development of prismatic structure
Secretory
What stage of an ameloblast’s life is described:
Enamel organ degenerates, eruption and exposure of enamel to oral cavity
Postmaturation
what is pre-dentine?
The organic matrix that makes up dentine before it is calcified
During what stage of an ameloblasts life cycle is BMP4 expressed?
Secretory
At what stage of tooth development does tooth shape determination occur?
Late cap stage and early bell stage
What determines tooth shape?
Differential rates of cell division/maturation
What feature of the developing tooth signals for tooth shape?
Dental papilla
What feature of the enamel organ determines the tooth shape and type?
Inner enamel epithelial cell maturation
What is the key transcription factor, found in the dental epithelium, that MUST be switched on in order for any tooth development to occur?
PITX2
Expression of what transcription factor drives incisive development?
MSX-1
Expression of what transcription factor drives molar development?
Barx-1 and Dlx1/2
What would happen to development of teeth if Dlx1/2 expression was switched off?
There will be no maxillary molars present
What would happen to teeth development if Barx-1 is over expressed?
The whole jaw would be covered in molars
What enzyme does the reduced enamel epithelium secrete to facilitate the breakdown of connective tissue to form am eruption pathway?
Protease
Which features of the developing tooth germ play a key role in bone resorption as the tooth erupts?
Reduced enamel epithelium and dental follicle
what two layers form the reduced enamel epithelium?
A layer of ameloblasts and the adjacent layer of cuboidal cells (outer enamel epithelium) from the dental lamina
what epithelium does the reduced enamel epithelium form?
Junctional epithelium
What common dental developments disturbances can occur in the initiation stage?
- hypodontia
- oligodontia
- anodontia
- supernumerary tooth or teeth
What common dental developments disturbances can occur in the bud stage?
Microdontia and macrodontia
What common dental developments disturbances can occur in the cap stage?
- dens in dente
- fusion
- gemination
What is dens in dente?
A rare developmental tooth anomaly characterised by invagination of the enamel organ into the dental papilla
What three components interact to from the root of a tooth?
- dental follicle
- Hertwig’s epithelial root sheath (HERS)
- dental papilla
Where do HERS cells originate from?
The apical region of the enamel organ (cervical loop)
what two cell layers does the enamel organ consist of?
The inner and outer enamel epithelium
What direction does HERS proliferate?
Apically
What direction does HERS disintegrate?
Cervically
what two processes do HERS cells influence?
- root dentinogenesis
- cementogenesis
What cells of tooth support does the dental follicle give rise to?
- Cementoblasts
- fibroblasts
- osteoblasts
What do Cementoblasts form?
Cementum
what do fibroblasts form?
PDL collagen fibres
What do osteoblasts form?
Alveolar bone
What are the three layers of the dental follicle?
- Inner investing layer ( becomes cementoblasts)
- loose connective tissue layer ( mainly fibroblasts)
- Outer layer (lines alveolar bone)
how do hyaline layers of Hopewell Smith form?
Enamel matrix proteins bind to dentine and predentine
What is the hyaline layer of Hopewell Smith?
The most peripheral layer of initially unmineralised dentin that forms immediately below the cementodentinal junction.
HERS produces what growth factors?
BMP4
EGF
TGF beta family
Transcription factor Shh
What process does HERS induce?
Odontoblast formation
what shape are fully differentiated odontoblasts in the coronal site (crown) of the tooth?
Columnar
what shape are fully differentiated odontoblasts in the root of the tooth?
Cuboidal
What enamel matrix proteins do HERS cells secrete on pre-dentine surface?
Amelogenins
What does HERS stand for?
Hertwig’s epithelial root sheath
How are cementoblasts formed?
By the induction of follicle cells that migrate to root surface of tooth and differentiate into cementoblasts
What happens when the cementum matrix mineralises?
Entraps PDL fibres (mainly type 1 collagen)
After disintegration of HERS, remnants are left over. What do they form?
Cell rests of Malassez in PDL
What are cell rests of Malassez in PDL?
Represent a group of cells in the PDL that have cystic potential
What two structures is the hyaline layer found between?
Dentine and cementum
What are the two main roles of the hyaline layer?
- Induces cementoblast formation
- Cements cementum to the tooth
What are the two types of cementogenesis?
- Acellular (primary)
- Cellular (secondary)
Where does the alveolar bone originate from?
The outer layer of condensed mesenchyme
Through what process to HERS cells form bone cells?
Osteogenic differentiation
what is the gubernacular canal?
An anatomical structure, which carries the gubernacular cord within it, that starts in the dental follicle and goes through to the alveolar bone crest behind the deciduous tooth
What is the main cell type found in the PDL?
Spindle-shaped fibroblasts
What two structures is the PDL found between?
Cementum and alveolar bone
In crown formation:
What does the epithelium form?
Enamel organ
In crown formation:
What cells does the enamel organ produce?
Ameloblasts
In crown formation:
What do ameloblasts form?
Enamel
In crown formation:
What does the ectomesenchyme form?
- dental papilla
- dental follicle
In crown formation:
What cells does the dental papilla produce?
Odontoblasts
In crown formation:
What do the odontoblasts form?
Dentine
In root formation:
What does the epithelium form?
Hertwig’s epithelial root sheath (HERS)
In root formation:
What does HERS form?
Hyaline layer of Hopewell Smith
In root formation:
What does the ectomesenchyme form?
-dental papilla
-dental follicle
In root formation:
What cells does the dental follicle produce?
- cementoblasts
- fibroblasts
- osteoblasts
Where does the permanent successor tend to sit in comparison to the primary predecessor tooth?
Lingually (lower) /palatally (upper)
What does ‘active’ eruption mean?
Bodily movement of the tooth
what does ‘passive’ eruption mean?
Uncovering of the tooth by apical gingival migration
What is the term used to describe the primary tooth eruptive movement?
Bloodless eruption
How could early loss of primary teeth delay the eruption of permanent teeth?
The cortical bone will heal fully, which is thick and more difficult for permanent teeth to erupt through
What are the 3 “PUSH’ eruption theories ?
- root formation
- bone formation
- fluid pressure
What are the 3 ‘PULL” theories of eruption, involving the PDL?
- collagen contraction
- fibroblast contraction
- fibroblast migration
What two theories of eruption are most likely to be correct?
Pull: by PDL fibroblasts
Push: hydrostatic pressure
In what direction do fibroblasts in the PDL move on eruption?
Cervically
What is bloodless eruption?
When a primary tooth passes through an epithelial-lined channel/pathway to erupt
What cells resorb primary teeth?
Odontoclasts
What can cementum be classed into?
Acellular and cellular cementum
what type of cementum is thin and covers the cervical root?
Acellular cementum
What type of cementum is thick and covers the apical root?
Cellular cementum
What percentages of cementum make up mineral, matrix and water?
Mineral: 65%
Matrix: 23%
Water: 12%
What role does HERS play in root formation?
Guides root formation and determines size, shape and number of tooth roots
When HERS cells secrete enamel matrix proteins onto dentine, what forms when they mineralise?
Hyaline layer of Hopewell Smith
What is the role of the hyaline layer?
- Induces cementoblast formation
- Cements cementum to the tooth
what is the traditional view of how cementum forms?
Cementum formed by cementoblasts derived from the dental follicle
What has new evidence found in regard to cementum formation?
At least some cementoblasts may be derived from HERS cells, undergoing EMT.
What happens upon cementum matrix mineralising?
PDL collagen fibres become trapped
What do remnants of HERS form, which have cystic potential?
Cells rests of Mallassez in PDL
Proteins in enamel can induce cementogensis. True or false?
True
What enamel matrix derivative us used clinically to induce cementogenesis?
Emdogain
What four layers make up the enamel organ?
- Inner enamel epithelium
- Outer enamel epithelium
- Stellate reticulum
- Stratum intermedium
What happens to the shape of maturing inner enamel epithelial cells?
They become more columnar and the nuclei polarise to basal end
What is the earliest week in utero that initiation stage of tooth development can occur?
6th week
What is the week in utero that bud stage of tooth development can occur?
8th week
What is the earliest week in utero that cap stage of tooth development can occur?
11th week
What week in utero can bell stage of tooth development occur?
14th week
What is the earliest week in utero that late bell/crown/appositional stage of tooth development can occur?
18th week
What genes cause selective tooth agenesis in humans?
PAX9 and MSX1