OE L12 Tooth Specification and Crown Development Flashcards
Which cells and structure form the jaws?
- Neural crest cells from posterior midbrain migrate to mandibular and maxillary processes (branchial arch 1)
- These processes later develop into the jaws
What happens if Hoxa-2 gene is knocked out?
Pharyngeal arch 1 structures are unaffected, but phayngeal arch 2 structures become arch 1 structures.
Are hox genes expressed in the head region?
No Hox gene expression in head region (absence of Hox is relevant to identifying the 1st pharyngeal arch). But there is expression of other homebox genes in the head.
What homeobox-containing genes are involved in patterning of dentition?
- Barx
- Dlx
- Lhx
- Pitx
- Msx
What are the role of the Dlx genes?
- Define a proximal-distal axis
- Define which jaw structures form (maxilla and mandible)
- Knocking out such genes changes jaw shape and size
What 3 pairs of Dlx genes are relevant to the head?
Dlx1/2
Dlx5/6
Dlx3/7
Which structure controls tooth morphogenesis?
The dental papilla.
Has a key role in epithelial-mesenchymal interactions responsible for tooth morophogenesis.
E.g. incisor enamel organ + molar papilla = molariform tooth
Molar enamel organ + incisor papilla = single cusp tooth
Information about tooth position is contained where?
Firstly in the oral epithelium, then later transferred to the ectomesenchyme.
What signalling restricts regions of mesenchyme that can express genes?
FGF8 signalling.
Only regions of mesenchyme adjacent to FGF8 expression can respond.
Mesenchyme can signal to oral epithelium, power shift from OE to mesenchyme in controlling tooth formation.
What is the odontogenic homeobox code?
Different combinations of odontogenic homeobox transcription factors are expressed at distinct times in spatially restricted areas of ectomesenchyme of the developing jaws.
This leads to distinct molecular fields leading to distinct tooth type and morphology.
Give examples of homeobox genes involved in tooth specification.
- Dlx1/2
- Msx2
- Barx1
- Alx3
- Msx1
What signals establish the molecular fields of the odontogenic homeobox code?
FGF-8 and BMP-4
expression establish molecular fields.
They induce expression of homeobox transcription factors in underlying mesenchyme and establishes spatial info that determines tooth type.
Which genes control tooth type in the maxilla?
- Incisors: Msx1 and Alx3
- Canines and premolars: Msx1 and Msx2
- Molars: Dlx1 and Dlx2
Which genes control tooth type in the mandible?
- Incisors: Msx1 and Alx3
- Canines and premolars: Msx1 and Msx2
- Molars: Barx1
Why does only one row of teeth form in each jaw? What prevents multiple rows of teeth forming?
- Anatomical boundary on the buccal side: the vestibular lamina (acts as natural barrier)
Why do extra rows of teeth not form on the lingual aspect of the jaws?
- Osr2 transcription factor is expressed in odontogenic mesenchyme on the lingual side
- Suppresses BMP-4/Msx1 signaling pathway
- Therefore molecular fields cannot be formed in these regions
What signalling pathway drives tooth bud formation?
- Shh signalling
- Found at embryonic day 11.5 in the tooth primordium
- Induces thickening of ectoderm to form tooth buds
Wnt-7b is a negative regulator of Shh and regulates tooth bud formation and isolates buds to specific areas along arch.
Why does cap stage mark a key event in crown formation?
- At cap stage the enamel knot forms
- Enamel knot is formed from differentiated IEE cells and acts as a transient signalling centre
- Primary enamel knot drives folding and growth of epithelium key to tooth shape
- Signalling molecules from primary enamel knot subsequently induce formation of secondary enamel knots at sites of cusps in molar teeth
What drives the transition from bud to cap stage of tooth development?
Signalling between epithelium and underlying mesenchyme tissue
Give examples of signalling factors expressed by the enamel knot.
- BMPs
- Shh
- FGFs
- Wnts
What signalling controls tooth number?
Wnt and BMP signalling
- Ectodin is a negative regulator of BMP and Wnt signalling and prevents inappropriate signalling
- Defects in ectodin causes supernumerary teeth
What important transmembrane protein regulates epithelial differentiation?
Ectodysplasin (Eda)
Where is Edar found?
Edar is only found in the enamel knot.
What does Eda-Edar signalling control?
- Size of dental placode
- Reprogrammes fate of epithelial cells
Describe hypohidrotic ectodermal dysplasia.
- Misshapen teeth
- Oligodontia
- Affects almost all ectodermal appendages
- Lack of sweat and sebaceous glands
What are the 3 main type of HED?
- X-linked HED (Eda effected)
- Autosomal HED (Edar effected)
- Anhidrotic ectodermal dysplasia with immune deficiency (NEMO effected)
What molecules are activators and inhibitors of crown shape regulation?
- BMP-4 acts as the activator. Induces enamel knot formation (each knot = 1 cusp)
- Inhibitors are Shh and FGFs. They repress knot formation and prevent activator expression.
What is tooth agenesis?
- Absence of 1 or more permanent teeth.
- Frequent occurence.
- Commonly due to haploinsufficiency of Msx1 and Pax9.
- Usually the last in a series that fails to form (e.g. lateral incisor, 2nd premolar, 3rd molar)- because the molecular field gets smaller and the tooth to fall off will be the last one.
