Tooth development

Dr. Gábor Varga

Department of Oral Biology February, 2016

Jawbone in cross section

CP cortical plates (compact lamellar bone) AB alveolar bone (spongy/bundle bone) BB basal bone ABP alveolar bone proper PDL periodontal ligament MS medullary spaces E enamel D dentin Tooth development (introduction)

• Bone formation (brief overview)

• Tooth development

• Common vs. different

• Stem cells (potential in dentistry)

Macromorphological structure of bone Macromorphological structure of bone

Osteon Havers lamella

Periosteum

Osteocyte

Compact bone Trabeculae (spongy bone) Bone formation 1 - intramembranous ossification Intramembranous ossification involves the replacement of sheet- like connective tissue membranes with bony tissue.

Bones formed in this manner are called intramembranous bones. They include certain flat bones of the skull and some of the irregular bones.

The future bones are first formed as connective tissue membranes.

Then osteoblasts migrate to the membranes and deposit bony matrix around themselves.

When the osteoblasts are surrounded by matrix they are called osteocytes. Intramembranous ossification in mandible – calcification occurs in a separate site from Merckel’s cartilage Bone formation 2 - Endochondral ossification The process of bone formation occurs in three stages, orchestrated by specialized bone cells that secrete and absorb materials as needed.

First, a soft cartilage-based foundation is laid, upon which mature bone will solidify.

Then, minerals containing calcium and phosphate are deposited throughout the foundation, creating a framework for the bone.

Finally, this raw material is sculpted and hardened into bone.

Missteps in this process can result in developmental defects and bone diseases Endochondral ossification: the epiphysis of a long bone. First is cartilage formation, then replaced by bone Major cell types of bone - the basis to achieve continuous renewal!!!) Molar Pulp Horn longitudinal section

the enamel covers the dentin Tooth development

LAMINA BUD STAGE CAP STAGE BELL STAGE ERUPTION Tooth development – details 1 Tooth development – details 2 Section of tooth – enamel and dentin formation Histologic slide showing a tooth bud

A: enamel organ B: dental papilla C: dental follicle Tooth bud formation Histologic slide of tooth in cap stage Histologic slide of tooth in early bell stage. Note cell organization

Histologic slide of tooth in late bell stage. Note disintegration of dental lamina at top Histologic slide of developing hard tissues. Ameloblasts form enamel, while odontoblasts form dentin. Histologic slide of tooth erupting into the mouth.

A: tooth B: gingiva C: bone D: periodontal ligaments Histologic slide of tooth. Note the tubular appearance of dentin.

A: enamel B: dentin Cross-section of tooth at root. Note clear, acellular appearance of cementum.

A: dentin B: cementum Sections of tooth undergoing development.

Neuronal development: a link to tooth development

Tucker, A., and Sharpe, P. The cutting-edge of mammalian development; how the embryo makes teeth. Nature reviews 5, 499, 2004. Enamel organ and dental papilla – Their interaction is crucial for tooth developments

Control of tooth shape – ectomesemchymal dominance

OBSERVE THAT TOOTH FORM IS DETERMINED BY THE DENTAL PAPILLA (ie the ectomesenchymal side)

Barx1 gene expression is strongly related to molar formation a) its suppression leads to incisor formation in molar area) b) its ectopic expression in incisor area leads to molar formation) Control of tissue differentiation – inductive action of mesenchyme OBSERVE THAT TISSUE TYPE FORMATION IS DETERMINED BY THE MESENCHYMAL SIDE Morphogenesis of tooth Tooth development is driven by communication between cells using signal molecules activating specific receptors Molecular components of control A model of the molecular regulation of tooth development from initiation to Epithelium crown morphogenesis

Mesenchyme The Runx2 gene is necessary for tooth development - In Runx2 knockout mice tooth developments stops at very early stage Oligodontia in a human patient with hypohydrotic ectodermal dysplasia (HED) - The ectodysplasin gene is crucial for tooth development Ectodysplasin stimulates tooth formation Effect of knock-out (KO) and Normal overexpression of ectodysplasin gene in mouse

Decreased number of Ectodysplasin molars KO -/-

Increased number of Ectodysplasin molars overexpression

Tooth development (summary)

• Bone formation (brief overview)

• Tooth development

• Common vs. Different

• Stem cells (potential in dentistry)