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The cutting-edge of mammalian development; how the embryo makes teeth

Key Points

  • Members of the fibroblast growth factor (FGF) and bone morphogenetic protein (BMP) families of protein signal from the oral epithelium to the underlying mesenchyme, patterning the presumptive incisor and molar fields in the developing mouth.

  • These signals result in the formation of a nested pattern of homeobox genes that are expressed in the mesenchyme, creating a homeobox code that determines tooth type.

  • Manipulation of this homeobox code causes transformations in tooth type, for example, from incisor to molar.

  • The expression of FGF and BMP proteins in the epithelium is refined by positive-feedback loops and mutual repression.

  • Tooth number can be manipulated by altering the level of ectodysplasin (EDA) signalling.

  • Tooth initiation involves interactions between Sonic hedgehog (SHH) and WNT signalling molecules in the oral epithelium.

  • The shape of the resulting tooth is coordinated by the enamel-knot signalling centre.

  • The cusp number in molar teeth can be manipulated by changing the level of EDA signalling.

  • Human dental disorders have been shown to involve many of the genes that have important roles in early tooth development in the mouse.

Abstract

A wealth of information has recently become available on the molecular signals that are required to form and pattern the dentition in the mouse, shedding light on how important decisions about tooth shape, tooth number and cusp (cone-shaped prominence) number are generated. This information, which has been gleaned principally from knockout mice and manipulation of organ cultures, has been used to identify the genes and developmental processes that underlie the many human disorders in which tooth development is defective. Mouse models of several of these syndromes have also indicated ways in which such conditions could be treated.

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Figure 1: Dentition in mice and humans.
Figure 2: Stages of tooth development.
Figure 3: Pattern of gene expression in the developing tooth.
Figure 4: Tooth type in cases of supernumerary teeth.
Figure 5: Examples of human dental disorders.

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Acknowledgements

Work in the authors' laboratories is supported by the Medical Research Council, the Biotechnology and Biological Sciences Research Council and the Wellcome Trust.

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Correspondence to Abigail Tucker or Paul Sharpe.

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Related links

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DATABASES

Entrez

Bapx1

Barx1

Bmp2

BMP4

Dlx2

Dlx5

Dlx6

Fgf4

Fgf8

Fgf9

Gsc

Islet1

Lhx6

Lhx7

Msx1

Msx2

p21

Pax9

Pitx2

Runx2

Runx3

Shh

Wnt7b

OMIM

Rieger syndrome type 1

Witkop syndrome

FURTHER INFORMATION

Gene Expression in Tooth

Glossary

ENAMEL

The hard outer covering of a tooth, consisting of apatite crystals that contain calcium and phosphate.

TELEOST FISH

A bony fish that belongs to the infraclass Teleostei (comprising more than 20,000 species), which includes nearly all the important food and game fish, and many aquarium fish.

MESENCHYME

Embryonic tissue that is composed of loosely organized, unpolarized cells of both mesodermal and ectodermal (for example, neural crest) origin, with a proteoglycan-rich extracellular matrix.

DENTIN (OR DENTINE)

The dense, yellowish tissue that forms the main part of tooth, between the enamel layer and the pulp cavity.

PLACODERM

An extinct class (Placodermi) of primitive fish, known only from fossil remains, that existed throughout the Devonian period (408–360 million years ago).

ECTOMESENCHYME

Mesenchyme that is derived from cranial neural-crest cells.

NEURAL CREST

A vertebrate-specific migratory cell type that derives from the dorsal-most aspect of the neural tube and contributes to many tissues, including the peripheral nervous system and cranium.

FATE MAPPING

A technique that is used to show how a cell or tissue moves and what it will become during normal development.

MANDIBLE

The lower jaw, derived from the first branchial arch.

MAXILLA

The rostral part of the first branchial arch, which joins with the nasal processes to form the upper jaw.

HAPLOINSUFFICIENCY

When loss of function of one gene copy leads to an abnormal phenotype.

HYPOPLASIA

The underdevelopment of a tissue or organ.

HYPOHIDROTIC

Impairment in the ability to perspire.

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Tucker, A., Sharpe, P. The cutting-edge of mammalian development; how the embryo makes teeth. Nat Rev Genet 5, 499–508 (2004). https://doi.org/10.1038/nrg1380

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