The document discusses the role of epithelial-mesenchymal interactions in tooth development, detailing the stages from tooth bud formation to the signaling factors involved. Key transcription factors like pax9 and msx1 are emphasized for their roles in tooth formation, with specific signals such as FGF8 and BMP4 being described for their positive and inhibitory effects. Overall, it highlights the reciprocal inductive interactions crucial for morphogenesis, including the formation of the enamel knot, essential for tooth structure development.

1. INDIAN DENTAL ACADEMY
Leader in continuing dental education
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2. Tooth Development
Karen Lyons, PhD
2641 MacDonald Research Laboratories
klyons@mednet.ucla.edu
825-5480
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3. epithelial mesenchymal interactions
epithelium
apical
basal
basal lamina
(ECM)
mesenchyme
tight junction
adherens unction
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4. Determination of tooth region
Oral ectoderm
(dental epithelium)
Jaw mesenchyme
Nonoral ectoderm
(nondental epithelium)
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5. Determination of tooth region
Dental lamina
(region of thickened
epithelium)
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6. Formation of tooth buds
oral ectoderm
dental mesenchyme
dental lamina
mesenchymal
Tooth placode condensation
Future crown
invagination
Bud stage
Future root
Bell stage
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7. Dental lamina
Bud stage
Bell stage
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8. Tissue recombination experiments reveal sources of
secreted factors that control tooth development at
different stages
oral ectoderm
oral ectoderm
?
jaw mesenchyme
nondental mesenchyme
nonoral ectoderm
nonoral ectoderm
?
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nondental mesenchyme
jaw mesenchyme

9. Ectodermal signals are required for the initiation of
tooth development
oral ectoderm
Tooth formation
nondental mesenchyme
nonoral ectoderm
no tooth formation
jaw mesenchyme
The ectodermal signal is a
secreted factor
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10. The sources of secreted signals that control tooth
development shift between epithelium and mesenchyme
Dental lamina
epithelium
Bud stage
mesenchyme
Bell stage
epithelium
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11. Pax9:
Transcription factor
PAX9+/- humans have oligodontia
Bud stage
Bell stage
Pax9-/- mice:
Tooth development is
arrested at Bud stage
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12. Msx1:
Transcription factor
Expressed in dental mesenchyme
Required for tooth formation
MSX1+/- Humans have
oligodontia
Msx1-/- mice:
Tooth development is arrested at Bud stage
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13. Pax9 and Msx1 are
expressed in dental
mesenchyme
Dental lamina (epithelium) is
the source of the secreted
signal(s) controlling tooth
formation
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14. Hypothesis: The dental lamina is the source of a
secreted signal that induces expression of Pax9 and
Msx1 in the underlying mesenchyme.
Pax9
Msx1
What is/are the secreted factor(s)?
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15. Secreted factors involved in tooth formation
Fibroblast growth factors (FGFs)
Bone morphogenetic proteins (BMPs)
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16. Ectodermal signals are required for the initiation of
tooth development
oral ectoderm
Mice lacking Pax-9 or
Msx1 do not form teeth
Pax-9
Msx1
jaw mesenchyme
Remove ectoderm
No expression of Pax-9
no tooth
or Msx1
development
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17. FGF8 is an epithelial signal required for initiation of
tooth development
oral ectoderm
Pax-9
Msx1
Mice lacking Pax-9 or
Msx1 do not form teeth
jaw mesenchyme
Control bead
Bead soaked in FGF8
Pax-9
No Pax-9 induction
Pax-9 induction
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18. FGF8 is expressed throughout entire dental epithelium
Dental epithelium
Pax-9
Pax-9
Jaw mesenchyme
Nondental
epithelium
Why doesn’t the a single continuous tooth form?
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19. Positioning of sites of tooth formation: antagonistic
signaling of FGF8 and BMP4
Dental epithelium
Pax-9
Pax-9
Jaw mesenchyme
(neural crest)
Sites of coexpression of
FGF8 and BMP4
FGF8
Pax9
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BMP4
Nondental
epithelium

20. The sources of secreted signals that control tooth
development shift between epithelium and mesenchyme
Dental lamina
Epithelium
FGF8 = +ve signal
BMP4 = antagonistic
Bud stage
mesenchyme
Bell stage
epithelium
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21. LEF1 is a
transcription
factor
The development of
teeth in LEF1-/mice is arrested at
the bud stage
LEF1 is expressed in the
epithelium
Source of secreted signal
controlling tooth formation
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22. Bud stage
BMP4 is an essential mesenchymal signal for tooth bud
development
How is BMP4
expression induced
in the mesenchyme?
LEF1
BMP4
condensed mesenchyme
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23. FGF8
Pax9
BMP4
Pax9 induces expression of BMP4 in the
condensing mesenchyme
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24. LEF1
Pax9
BMP4
BMP4 produced in the dental mesenchyme induces
LEF1 expression in the epithelium
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25. The sources of secreted signals that control tooth
development shift between epithelium and mesenchyme
Dental lamina
Epithelium
FGF8 = +ve signal
BMP4 = antagonistic
Bud stage
Mesenchyme
BMP4 = +ve signal
Bell stage
epithelium
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26. Reciprocal signaling during early stages of
tooth development
Bud stage
Initiation stage
Epithelial Signaling
BMP4
(+ FGF8)
Mesenchymal signaling
FGF8
LEF1
Pax-9
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BMP4

27. Control of tooth shape
epithelium
molar
mesenchyme
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incisor

28. The enamel knot is the source of secreted signals
that cause proliferation of neighorbing epithelial
cells
Bud stage
mesenchyme
BMP4 = +ve signal
Bell stage
enamel knot
The enamel knot is induced by BMP4
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29. The enamel knot is
induced by BMP4
BMP4
The enamel knot
produces FGFs that
stimulate
proliferation of
adjacent epithelium
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30. SUMMARY
Reciprocal inductive interactions between
epithelium and mesenchyme control tooth
morphogenesis
FGF8 is an epithelial signal that positively
regulates morphogenesis at the initiation stage
FGF8 is an epithelial signal produced by the
enamel knot that stimulates proliferation of
neighboring epithelial cells to control cusp
formation
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31. BMP4 is an inhibitory signal (secreted by epithelium)
at early stages of tooth initiation
BMP4 is a stimulatory signal (secreted by mesenchyme)
at the Bud stage
BMP4 induces the formation of the enamel knot
Pax9, Msx1, and LEF1 are transcription factors that
are required for tooth morphogenesis
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32. Thank you
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