The life cycle of ameloblast and

correlation to dental abnormalities

By/ Rana Helmy Abd el-baky

Prof Dr/ Heba Ahmed Adawy

Ass prof/ Nehad Abd El-mawgod
•Ameloblasts are cells that form the hardest tissue of the body, the
enamel.
•These cells can give rise to multiple diseases such as developmental
disorders, neoplasms, and cysts when faced with inappropriate
stimuli.
 The developmental aspect of ameloblasts

• Ameloblasts are responsible for enamel formation in the teeth.

• They are derived from preameloblasts, Preameloblasts are the

derivatives of neural crest cells.

• Neural crest cells are generated from the ectoderm.

• There are three germ layers from which all tissues of the body are
formed.

• These germ layers are namely (ectoderm, mesoderm, and

endoderm).
•Ameloblasts exist in the human body from the beginning of enamel
formation till its completion.
•After completion of enamel formation, they become part of reduced
enamel epithelium, which forms the primary attachment epithelium as
the tooth erupts in the oral cavity.
•After this, ameloblasts no longer exist in the body. Therefore, enamel
cannot be repaired or regenerated.
•Tooth development begins during the 6th week of intrauterine life
when the first sign of tooth development is seen.
•Various stages of tooth development are the bud stage, cap stage,
bell stage, and advanced bell stage.
•This tooth‑forming apparatus is called the enamel organ.
•In the bell and advance bell stage, the enamel organ becomes distinct.

•It assumes the shape of a bell. The outer aspect of a bell stage shows
outer enamel epithelium or external dental epithelium.
•The inner aspect of a bell is lined by cells of the inner enamel
epithelium.
•The meeting point of the inner and outer enamel epithelium is called
the cervical loop.
•It is the cells of inner enamel epithelium that become pre-ameloblasts
in the bell stage and become ameloblasts in the advanced bell stage
 Ameloblasts and matrix deposition

• Secretory ameloblasts (SABs) are tall, columnar, and polarized

cells.

• SABs involve growth and elongation of the cytoplasm, a change in

polarity, and sequential development of organelles.
• The undifferentiated cells of the ameloblastic layer initially
produce material for internal use.

• As soon as the enamel matrix begins to be deposited at the distal

surface, ameloblasts recede, leaving the cytoplasmic extension
(Tomes process) in the early calcifying enamel
•Amelogenesis is the formation of enamel by ameloblasts.

•The major proteins secreted by ameloblasts are (amelogenins,

enamelins, ameloblastins, and tuftelins) which are produced by the
ameloblasts into the extracellular space.
•Ameloblastin simultaneously halts the proliferation of ameloblasts,
whereas enamelins and amelogenins are essential for the deposition of
hydroxyapatite crystals.
•Ameloblastins and amelogenins are removed during maturation
when ameloblasts produce proteinases (e.g., MMP), cleaving these
substances.
•The debris is consumed by ameloblasts, and the enamel turns into
an extremely mineralized tissue.
•Half of the ameloblasts undergo apoptosis during amelogenesis; the
rest die after the process ends.
•Therefore, amelogenesis stops at the point of tooth eruption, and
there is no production of secondary or regenerative enamel.
 Intracellular control and extracellular control in
ameloblasts

• Preameloblasts differentiation into SABs relies on a highly regulated

network of interactions between conserved signal transduction
pathways, including members of the bone morphogenetic protein
transforming growth factor‑beta, Notch, and mitogen ‑activated protein
kinase (MAPK) pathways to coordinate all aspects of ameloblasts in
intracellular processes and their social contexts.
 Ameloblasts in Disease
• The enamel phenotype resulting from different types of injuries during
amelogenesis will vary depending on the type of stress as well as the
duration and intensity of the influence.

• Environmental stressors of short span (e.g., fever) often cause

localized deformities, whereas chronic stressors (e.g., elevated
fluoride exposure) are more likely to be associated with generalized
defects.
 Genetic disorders of ameloblasts

• There are several classes of genes in ameloblasts’ life cycle

elucidating the molecular regulatory cascades.
 Junctional epidermolysis bullosa:

• It is due to weakness in the cell‑to‑cell adhesion.

• The abnormal proteins from defective genes result in fragile skin

that blisters.

• Interestingly, some mutations in genes such as laminin subunit beta

3 can result only in enamel hypoplasia (enamel phenotype).
 Tricho‑dento‑osseous syndrome:

• It is related to kinky curly hair at birth, dense ‑thick bone,

generalized thin and/or pitted enamel, and large pulp chambers.

• Mutations in the p63 gene, an essential gene in cell growth, causes

a variety of ectodermal dysplasia (ED) syndromes (e.g., Rapp
Hodkins syndrome, ectrodactyly, ED cleft syndrome), all of which
can have enamel defects.
 Jalili syndrome:

• Affected individuals have cone‑rod dystrophy in the eyes and

enamel that has a brown appearance and is hypomineralized.

• This condition is caused by mutations in the cyclin and domain

cystathionine‑synthase (CBS) divalent metal transport mediator 4
genes (CNNM4) (cyclin and CBS domain divalent metal cation
transport mediator 4) that may play a role in metal ‑ion transport
 Cystic fibrosis (CF):

• It is caused by mutations in the CFTR gene (CF transmembrane

conductance regulator) that are involved in regulating ion
movement and pH regulation. Clinical evaluation of humans with
CF found a high percentage of affected individuals had associated
enamel defects of varying severity.
 Amelogenesis imperfecta:

• Hereditary nonsyndromic conditions primarily affecting the enamel

are referred to as amelogenesis imperfecta (AI).
• Enamel mineralization relies on Ca availability provided by Ca
2+ 2+

release‑activated by Ca (CRAC) channels.

2+
•CRAC channels are modulated by the endoplasmic reticulum Ca2 +
sensor stromal interaction molecule 1 (STIM1) which gates the pore
subunit of the channel known as ORAI calcium release‑activated
calcium modulator 1 (ORAI1) found in the plasma membrane, to enable
sustained Ca2 + influx. Mutations in the STIM1 and ORAI1 genes
result in CRAC channelopathy, an ensemble of diseases including
immunodeficiency, muscular hypotonia, ED with defects in sweat gland
function, and abnormal enamel mineralization similar to AI.
 Hereditary ectodermal dysplasia:

• Patients with mutations in STIM1 and ORAI1 have been

described as presenting with ED, similar to those in ED patients.
 Enamel hypoplasia:

• Enamel hypoplasia may develop on the tooth due to instabilities

during the secretory stage of amelogenesis. Injuries during the
later stages of enamel formation, calcification, and maturation may
result in enamel opacities.
•Variability in the development of the defects is caused by the
selective involvement of only those ameloblasts active at the time of
disturbance. Some of the affected ameloblasts die and discontinue
secreting enamel matrix, while other cells continue to secrete normal
enamel over the defective areas.
•Enamel hypoplasia is associated with Usher syndrome, Ellis Van
Creveld syndrome, fluorosis, fever, starvation, excess fluoride
exposure, trauma, hypoxia infection, tetracyclines, low birth
weight, and hyperbilirubinemia.
 Nonhereditary Disorders of Ameloblasts

Odontogenic tumors:

Odontogenic Cysts:
 Odontogenic tumors:

Ameloblastoma:
• Ameloblastoma is a slow‑growing, locally invasive, benign
epithelial odontogenic neoplasm. It is thought to arise from
SOX2‑expressing dental lamina epithelium and remnants of the
tooth‑forming enamel organ.
• The tumor exhibits the proliferation of epithelial cells resembling
pre-ameloblasts on a basement membrane.
 Ameloblastic fibroma:

• Ameloblastic fibroma is a tumor of odontogenic origin characterized

by the proliferation of both epithelial and mesenchymal odontogenic
tissues without the formation of hard tissue structures.
• The epithelial (ameloblastic) component consists of islands and cords
of odontogenic epithelium that often resemble the dental lamina of
early tooth development.
• There is usually sufficient differentiation of the peripheral cells of
these islands, and characteristic high cuboidal or columnar
ameloblasts can be recognized.
 Malignant ameloblastoma:

• The terms malignant ameloblastoma and ameloblastic carcinoma

have been used interchangeably for these variants in the past.
• Malignant ameloblastoma and ameloblastic carcinoma are two
distinct types of ameloblastoma.
• Ameloblastic carcinoma is locally aggressive and may or may not
undergo regional lymph node metastasis, whereas malignant
ameloblastoma would show metastasis.
 Odontomes:

• Tooth‑like structures with central cores of the pulp tissue are seen
microscopically.

• They consist of haphazardly encased pulp in dentin shells and

partially covered by conglomerates of dentin, enamel, enamel
matrix, enamel surrounded by a fibrous capsule similar to the
cementum, and pulp tissue follicle surrounding a normal tooth .
 Odontogenic Cysts

Dentigerous cysts:
• The pathogenesis of dentigerous cysts is indistinct.
• It is proposed that dentigerous cysts develop from abnormal fluid
accumulation between the reduced enamel epithelium and the
enamel or within the enamel organ.
• The proliferation of the epithelium may be induced by osmotic
pressure from the fluid‑filled sac when the tooth is impacted.
  Eruption cysts:

• It is a soft tissue analog of the

dentigerous cyst.
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Thank you