Tooth development /certified fixed orthodontic courses by Indian dental academy

INDIAN DENTAL ACADEMY
Leader in continuing dental education
www.indiandentalacademy.com


Tooth Development

Karen Lyons, PhD
2641 MacDonald Research Laboratories
klyons@mednet.ucla.edu
825-5480

epithelial mesenchymal interactions
epithelium

apical

basal
basal lamina
(ECM)
mesenchyme
tight junction
adherens unction

Determination of tooth region
Oral ectoderm
(dental epithelium)

Jaw mesenchyme

Nonoral ectoderm
(nondental epithelium)

Determination of tooth region
Dental lamina
(region of thickened
epithelium)


Formation of tooth buds
oral ectoderm

dental mesenchyme

dental lamina
mesenchymal
Tooth placode condensation

Future crown
invagination

Bud stage

Future root
Bell stage

Dental lamina

Bud stage

Bell stage

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
?



jaw mesenchyme

Ectodermal signals are required for the initiation of
tooth development
oral ectoderm

Tooth formation
nonoral ectoderm
no tooth formation

jaw mesenchyme

The ectodermal signal is a
secreted factor

The sources of secreted signals that control tooth
development shift between epithelium and mesenchyme
Dental lamina
epithelium

Bud stage
mesenchyme

Bell stage
epithelium

Pax9:

Transcription factor

PAX9+/- humans have oligodontia

Bud stage

Bell stage
Pax9-/- mice:
Tooth development is
arrested at Bud stage


Msx1:

Transcription factor
Expressed in dental mesenchyme
Required for tooth formation

MSX1+/- Humans have
oligodontia

Msx1-/- mice:
Tooth development is arrested at Bud stage

Pax9 and Msx1 are
expressed in dental
mesenchyme

Dental lamina (epithelium) is
the source of the secreted
signal(s) controlling tooth
formation


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)?

Secreted factors involved in tooth formation
Fibroblast growth factors (FGFs)

Bone morphogenetic proteins (BMPs)


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

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


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?

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


BMP4

Nondental
epithelium

Dental lamina
Epithelium
FGF8 = +ve signal
BMP4 = antagonistic
Bud stage
mesenchyme

Bell stage
epithelium

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

Bud stage
BMP4 is an essential mesenchymal signal for tooth bud
development

How is BMP4
expression induced
in the mesenchyme?

LEF1
BMP4

condensed mesenchyme

FGF8
Pax9

BMP4

Pax9 induces expression of BMP4 in the
condensing mesenchyme

LEF1

Pax9

BMP4

BMP4 produced in the dental mesenchyme induces
LEF1 expression in the epithelium

Dental lamina
Epithelium
FGF8 = +ve signal
BMP4 = antagonistic
Bud stage
Mesenchyme
BMP4 = +ve signal
Bell stage
epithelium

Reciprocal signaling during early stages of
tooth development
Bud stage

Initiation stage

Epithelial Signaling

BMP4
(+ FGF8)

Mesenchymal signaling

FGF8
LEF1
Pax-9

BMP4

Control of tooth shape

epithelium

molar
mesenchyme


incisor

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

The enamel knot is
induced by BMP4
BMP4

The enamel knot
produces FGFs that
stimulate
proliferation of
adjacent epithelium

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

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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Tooth development /certified fixed orthodontic courses by Indian dental academy

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