Early + Late Tooth Development

• what is ondontogenesis?

  tooth development
• when do deciduous teeth begin to develop?

  weeks 6-7 in-utero life
• when do permanent teeth begin to develop?

  weeks 14 in-utero life
• what two tissue components does the development of teeth begin from?

  - primitive oral epithelium (derived from ectoderm)

  - ectomesenchyme (derived from craniofacial neural crest cells that migrate from the developing midbrain and the first two rhombomeres into the first branchial arch)
• how do craniofacial neural crest cells become the ectomesenchyme?

  craniofacial neural crest cells undergo an epithelial-to-mesenchymal transition (EMT).

  -> The cells originate from ectodermal epithelial and they transform into mesenchymal cells that have a distinct shape and migratory properties.

  
  

  (it is a mesenchyme derived from ectoderm and so it is called ectomesenchyme)
• craniofacial neural crest cells are multipotent. TRUE/FALSE

  TRUE
• how does primitive oral epithelium and ectomesenchyme work together for tooth development?

  they instruct each other on the formation and location for the specialised teeth
• signals from which tissue leads to tooth initiation?

  the oral ectoderm
• describe the initiation stage of tooth development

  • primitive oral epithelium thickens into primary epithelial bands (one on each jaw)

  - thickening happens because as new cells are made they are stacked vertically instead of parallelly to the epithelium

  
  

  • each primary epithelial band splits into two:

  - inner (lingual) dental lamina

  - outer (buccal) vestibular lamina

  
  

  • the vestibular lamina hollows and forms the vestibule of the mouth (space between alveolar portions of the jaws, lips, and cheeks)

  
  

  • signal proteins such as FGFs, BMPs, and EDA, cause the cells within the dental lamina to start proliferating and to invaginate into the positions that correspond to the positions of the future teeth -> This forms dental placodes (enlarged projections)

  
  

  • as the dental placodes continue to proliferate, the tooth undergoes morphogenesis (which results in different teeth shapes)
• the expression of what transcription factor is associated with dental placodes?

  Pax9

  - so it labels the sites of tooth development
• what are the stages of morphogenesis?

  bud, cap, and bell
• what happens during the bud stage of morphogenesis?

  • the dental placodes proliferate to form a bud-like structure, known as the tooth bud, that is attached to the oral epithelium by the dental lamina

  
  

  • the ectomesenchymal cells start to cluster around the tooth bud resulting in condensation of the ectomesenchyme (especially right beneath the bud).

  
  

  • eventually, due to the tooth bud cells different growth rates, invagination occurs. This means the tooth bud becomes a cap shape.
• what are the 2 types of cells the tooth bud is made of?

  - outer layer of low columnar cells

  - inner bundle of polygonal cells
• what does it mean when we say that the tooth bud has a differential proliferation of cells?

  different parts of the bud grow at different rates

  
  

  - cells are center proliferate slower than cells in the periphery
• what is the signaling pathway essential for bud to cap transition?

  BMP (bone morphogenetic protein) signaling:

  - BMP are secreted in the extracellular space

  - they bind to type 1 receptors which will recruit the type 2 receptors

  - this leads to the phosphorylation of the receptor complex

  - the signal is transduced to the nucleus and lead to the activation of the transition of target genes

  
  

  -------------> requirement for BMP signaling starts at initiation:

  - BMP4 is secreted by dental epithelial cells

  - they signal to cells in dental mesenchyme which leads to the transcription factor Msx1 being expressed with Pax9 to induce the secretion of BMP4.

  - BMP4 diffuses form mesenchyme to epithelium; this leads to the formation of the primary enamel knot promoting the transition from bud stage to cap stage
• describe the cap during the cap stage of morphogenesis

  3 different types of epithelial can be seen; forming the enamel organ (the epithelial part of the tooth germ):

  
  

  1. inner enamel epithelium

  2. outer enamel epithelium

  3. stellate reticulum
• describe the inner enamel epithelium of the enamel organ

  layer of low columnar cells that line the inner surface of the caps central depression
• describe the outer enamel epithelium of the enamel organ


  layer of cuboidal cells that line the sides of the cap on the outside
• describe the stellate reticulum of the enamel organ

  - a bunch of cells that are linked by desmosomes.

  - they secrete glycosaminoglycans into the extracellular space
• what happens during the cap stage of morphogenesis?

  • the glycosaminoglycans secreted by the stellate reticulum cells attract water into the extracellular space. The water pushes on the cell membranes of the stellate cells turning them into the shape of a star.

  
  

  • the ectomesenchymal cells surrounding the enamel organ continue to accumulate (especially near the invagination of the cap)

  ----> the dense condensation of the ectomesenchymal cells beneath the cap is called the dental papilla

  ----> the accumulation of the ectomesenchymal cells that encircle the dental papilla and the enamel organ is called the dental sac or dental follicle
• what are the 3 layers of the dental follicle?

  - inner layer

  - loose connective tissue

  - outer layer
• what do the nondividing cells of the enamel organ do?

  - they sit in the inner enamel epithelium.

  - they are known as the enamel knots

  - the enamel knot is a signalling center that regulates the formation of the cusps of the tooth
• what signaling molecules does the enamel knot produce?

  BMPs

  FGFs

  Wnts

  Shh
• how do the enamel knots determine the formation of the cusps of the tooth?

  the number and location of enamel knots determine the number and location of cusps in the developing tooth.
• when is the enamel knot present?

  only during the cap stage

  -> It is eliminated by programmed cell death (apoptosis) after the cap stage
• how many enamel knots can be present during the cap stage?

  both mono-cusped teeth (incisors and canines) and multi-cusped teeth (molars and premolars) have one single primary enamel knot in the cap stage
• what does the enamel knot mark the position of on molars?

  the first buccal cusp
• during the bell stage, can more enamel knots be produced?

  more enamel knots form in multicuspid teeth only

  (the number of enamel knots determines the number of cusps: secondary, tertiary...)
• what happens during the bell stage of morphogenesis?

  • as the enamel organ continues to grow, the invagination in the cap deepens forming the cervical loop at the tip of the invaginating epithelium where the inner and outer epithelium meet

  
  

  • within the enamel organ a few epithelium cells between the inner epithelium and stellate reticulum differentiate into a layer of spindle-shaped cells known as stratum intermedium.

  
  

  • the stellate reticulum starts to collapse, reducing the distance between the inner and outer enamel epithelium

  
  

  • the tooth germ epithelium then forms the bell-shaped structure that will become the crown of the tooth.

  
  

  • morpho-differentiation and histodifferentiation occurs
• describe morpho-differentiation during the bell stage of morphogenesis

  the future shape of the crown is determined
• describe histodifferentiation during the bell stage of morphogenesis

  the conversion of cells of the dental organ into specialised cells.

  -> such as ameloblasts which produce enamel and

  odontoblasts which produce dentin
• how do ameloblasts and odontoblasts work together?

  ameloblasts and odontoblasts give each other signals to differentiate

  -> when odontoblasts lay down dentin, it triggers the formation of enamel by triggering the formation of mature ameloblasts from preameloblasts
• what cells differentiate into ameloblasts?

  inner enamel epithelium cells

  -> differentiates into preameloblasts and then mature ameloblasts
• what do ameloblasts do?

  lay down enamel
• how do ameloblasts get nutrients?

  because the stellate reticulum starts to collapse during the bell stage and the distance between the inner and outer enamel epithelium is reduced. This brings the blood vessels surrounding the tooth germ closer to the active ameloblasts enabling them to get nutrients.
• what cells differentiate into odontoblasts?

  dental papilla cells
• what do odontoblasts do?


  produce dentin
• what is the mineralised tissue in the tooth?

  enamel and dentin
• what is the non-mineralised tissue in the tooth?

  dental pulp
• what happens to the dental lamina as ameloblasts and odontoblasts form the mineralised matrix?

  It disintegrates. This completely deataches the tooth germ from the dental epithelium

  
  

  -> sometimes when it disintegrates, it may leave behind nests of epithelial cells (epithelial pearls); which can give rise o a bunch of abnormalities in the future- for e.g. supernumerary teeth, odontoma, and eruption cysts.