Tooth Morphogenesis

• what does overexpression of Edar in tooth development lead to?

  - tooth cusps can develop if receptor activated

  - additional sharp cusps after overactivation of Eda pathway in wildtype tooth germs

  
• how does a defect in primary enamel knot formation lead to less cusps?

  = smaller / misshapen primary enamel knot

  = defective formation of secondary enamel knots

  = less cusps
• experimental work

  
  

  in a mice, what can happen to the enamel knot if the mice has a defect in Eda, Edar, or Edaradd?


  - the enamel knot does not form

  - the enamel knot forms but is abnormal in shape

  - the enamel knot forms but it is reduced in size
• what happens to patients that have a defect in Eda, Edar, or Edaradd?


  they have X-linked hypohidrotic ectodermal dysplasia

  = reduced teeth and flattened cusps

  
• What does the Eda signalling pathway look like?

  - Eda is expressed in the collar region of the tooth germ

  - Eda binds to its receptor called Edar (which is only found in the enamel knot cells)

  - Edaradd is the internal region of the Eda receptor and it transduces the signal

  
• what is the Eda signaling pathway?

  The EDA gene provides instructions for making a protein called ectodysplasin A. This protein is part of a signaling pathway that plays an important role in development before birth.
• experimental work

  
  

  what happened when the alveolar bone was removed from a developing tooth?

  the tooth grew much larger due to increased proliferation when the alveolar bone was removed
• why is it good that the tooth sizes are limited?

  it ensures that all the teeth fit in the jaw
• What limits the size of teeth?

  the alveolar bone
• why do some people have cusp of carabelli?

  It is due to variations in developmental timing or spacing of enamel knots (cusps far apart) + large tooth
• how is the height of the cusps on the tooth linked to the timing of initiation of secondary enamel knots?

  earlier formed cusps are taller because the enamel knot would have been signaling for much longer and telling the cells to proliferate for longer than the later ones
• what does the number / arrangement of secondary enamel knots tell us?

  number / arrangement of cusps
• what does increasing the number of enamel knots do to the number of cusps?

  it increases the number of cusps
• incisors go on to develop secondary and tertiary enamel knots

  TRUE/FALSE

  FALSE

  molars go on to develop secondary and tertiary enamel knots
• both molars and incisors have primary enamel knots.

  TRUE/FALSE

  TRUE
• what are secondary and tertiary enamel knots for?

  further cusp formation
• what stimulates cell death in the primary enamel knot and silencing of the signaling center?

  Bmp4
• what happens to the primary enamel knot after the cap shape is formed?

  death of the enamel knot (apoptosis)
• why is the primary enamel knot a transient structure?
• what two things are required for the tooth germ to change shape?

  - cell movement and cell shape rearrangements thanks to focal adhesion kinases

  - proliferation differences
• other than proliferation, what else is needed to change the tooth germs shape from bed to cap?

  focal adhesion kinases which allows the cells to move around and change shape

  -> If the focal adhesion kinase inhibitor is added, proliferation occurs so the toot germ gets larger but the cap shape does not form.
• what does inhibition of proliferation lead to?

  the cap stage like tooth germ is still able to form

  -> so proliferation is not the only thing that causes the change in the tooth germs shape
• what does proliferation caused by the primary enamel knot result in?

  There is high proliferation outside the enamel knot and low proliferation within the enamel knot

  -> This results in a folding of the dental epithelium which changes the bud shape to the cap shape
• the enamel knot expresses growth factors. what prevents it from growing itself?

  it does not express the receptors complementary to the growth factors and so cannot respond to its own signals
• give examples of what signaling molecules the primary enamel knot produces

  Fgf4 and shh stimulate growth and proliferation of the dental epithelium
• when is the primary enamel knot formed?

  at the bud stage of tooth development by signals from the mesenchyme
• what is the primary enamel knot?

  a group of nondividing cells that act as a signaling center that regulates the formation of the cusps of the tooth
• experimental work

  
  

  What was the result of experimentally trying to grow a tooth in the canine region of the mouth of a mouse? Comment on the findings.

  It produced a premolar-like tooth.

  This shows that although mice don't have premolar teeth, the information regarding their patterning is still in place ( they still have the code for the tooth in that region of the jaw).
• experimental work

  
  

  What do the levels of Barx1 define in a shrew (mouse-like animal)?

  the tooth cusp numbers

  
  

  less expression of Barx1= less cusps

  (there is a lot of Barx1 expressed in the presumptive molar region, and slightly less in the premolar region but it is still present)
• what is BARX1?

  BARX homeobox 1 is a protein that in humans is encoded by the BARX1 gene
• What does tooth type depend on?

  The expression of homeobox genes in the mesenchyme into which the tooth germ invaginates
• what is the role of the homeobox in tooth development?

  The combination of homeobox genes expressed is the code that specifies the type of tooth that has to be formed in that specific area

  
• what is a homeobox?

  A homeobox is a DNA sequence found within genes (homeobox genes) that regulates developmental processes in animals, fungi, and plants.
• what does it mean when we say humans are heterodont?

  human teeth are different in shape and size:

  we have incisors, canines, premolars and molars.