Talk:Integumentary System - Tooth Development

http://embryology.med.unsw.edu.au/Notes/skin10.htm

http://www.ncbi.nlm.nih.gov/pubmed/19750524

Cell fate determination during tooth development and regeneration.

"Teeth arise from sequential and reciprocal interactions between the oral epithelium and the underlying cranial neural crest-derived mesenchyme. Their formation involves a precisely orchestrated series of molecular and morphogenetic events, and gives us the opportunity to discover and understand the nature of the signals that direct cell fates and patterning. For that reason, it is important to elucidate how signaling factors work together in a defined number of cells to generate the diverse and precise patterned structures of the mature functional teeth. Over the last decade, substantial research efforts have been directed toward elucidating the molecular mechanisms that control cell fate decisions during tooth development. These efforts have contributed toward the increased knowledge on dental stem cells, and observation of the molecular similarities that exist between tooth development and regeneration."

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Human Tooth Pattern

File:Deciduousteeth.jpg	Deciduous teeth (20): four incisors, two canines, and four molars, in each jaw.
	Permanent teeth (32): four incisors, two canines, four premolars, and six molars, in each jaw.

Tooth Stages

There are 4 morphological stages describing early tooth development: bud, cap, bell, and terminal differentiation.

bud

cap

bell

terminal differentiation

Tooth Cells

Ameloblasts - Pre-ameloblasts differentiate from the inner enamel epithelium. Cells secrete enamel

Cementoblasts

Odontoblasts - neural crest-derived mesenchymal cells which differentiate under the influence of the enamel epithelium. Cells secrete dentin.

Epithelial Mesenchymal Interaction

• local ectodermal thickening expresses several signaling molecules
• these in turn signal to the underlying mesenchyme triggering mesenchymal condensation

(epithelially expressed Bmp4 induces Msx1 and Lef1 as well as itself in the underlying mesenchyme)

Four epithelial signaling molecules, Bmp2, Shh, Wnt10a, and Wnt10b, in the early inductive cascade, each signal has a distinct molecular action on the jaw mesenchyme.

Mouse (E11.0 and E12.0) - all four genes are specifically expressed in the epithelium.

Shh and Wnt10b induce general Hedgehog and Wnt targets, Ptc and Gli for Shh and Lef1 for Wnt10b,

Bmp2 is able to induce tooth-specific expression of Msx1.

(Text above modified from: Hélène R. Dassule and Andrew P. McMahon Developmental Biology, v 202, n 2, October 15, 1998, p215-227)

(More? [mechanism1.htm Developmental Mechanism - Epithelial Mesenchymal Interaction])

Periodontal Ligament (PDL)

The tooth is not anchored directly onto its bony socket (alveolar bone) but held in place by the periodontal ligament (PDL), a specialized connective tissue structure that surrounds the tooth root coating of cementum.

The additional roles of the PDL are to also act as; a shock absorber, transmitter of chewing forces (from tooth to bone), sensory information (heat, cold, pressure and pain).

The collagen fiber bundles within the ligament are called "Sharpey’s fibres".

Cementum (from investing layer of the dental follicle) is contiguous layer with the periodontal ligament on one surface and firmly adherent to dentine on the other surface.

(More? [skmus.htm Musculoskeletal Development])

Molecular Tooth Development

More than 300 genes have been associated with tooth development including: BMP4, FGF8, MSX1, MSX2, PAX9, PITX2, SHOX2, Delta/Notch, Hox-8, Runx2

Most recent review in Developmental Dynamics by Lin D, Huang Y, He F, Gu S, Zhang G, Chen Y, Zhang Y. Expression survey of genes critical for tooth development in the human embryonic tooth germ. Dev Dyn. 2007 Mar 29.

Amelogenin - abundant protein secreted by ameloblasts which is a major component of tooth enamel.

The papers below are from UNSW Embryology (version 3), information requires updating.

Bone Morphogenic Protein (BMP) / Fibroblast Growth Factor (FGF)

Growth factors in the BMP- and FGF-families are expressed in dental epithelium during initiation of tooth development and their effects on the underlying mesenchyme mimic those of the epithelium. They upregulate the expression of many genes, including the homeobox-containing Msx-1 and Msx-2, and stimulate cell proliferation suggesting that they may act as epithelial signals transmitting epithelial-mesenchymal interactions. During subsequent morphogenesis, when the characteristic shapes of individual teeth develop as a result from folding of the dental epithelium, several signal molecules including Sonic hedgehog, Bmps-2, 4, 7 and Fgf-4 are expressed specifically in restricted and transient epithelial cell clusters, called enamel knots.

(Text: Irma Thesleff and Carin Sahlberg Seminars in Cell & Developmental Biology, v 7, n 2, April, 1996, p185-193)

Delta/Notch

The expression pattern of Delta 1 in ameloblasts and odontoblasts is complementary to Notch1, Notch2, and Notch3 expression in adjacent epithelial and mesenchymal cells. Notch1 and Notch2 are upregulated in explants of dental mesenchyme adjacent to implanted cells expressing Delta1, suggesting that feedback regulation by Delta-Notch signaling ensures the spatial segregation of Notch receptors and ligands. TGF1 and BMPs induce Delta1 expression in dental mesenchyme explants at the stage at which Delta1 is upregulated in vivo, but not at earlier stages. In contrast to the Notch family receptors and their ligand Jagged1, expression of Delta1 in the tooth germ is not affected by epithelial-mesenchymal interactions, showing that the Notch receptors and their two ligands Jagged1 and Delta1 are subject to different regulations.

Text: Mitsiadis etal Developmental Biology,v 204, n 2, December 15, 1998, p420-431

Abnormalities

adontia - total lack of tooth development.

amelogenesis imperfecta - abnormal tooth enamel formation (AMELX, ENAM, KLK4, MMP20).

dentinogenesis imperfecta - discoloured teeth with an opalescent sheen, dentin does not support enamel (dentin sialophosphoprotein mutation)

dens evaginatus - dental anomaly mainly affecting premolars in people of Mongolian origin.

hypodontia - lack of development of one or more teeth.

hypohidrotic ectodermal dysplasia - maldevelopment of one or more ectodermal-derived tissues.

microdontia - small teeth.

WWWLinks

University of Helsinki Gene Expression in Tooth

American Dental Association Overview - Tooth

Columbia University Medical Centre Illustrations: How a Tooth Decays

Merck Tooth disorders

Nemours Foundation Teething Tots

References

(More? [../Refer/skin/teeth.htm Tooth Development References])

Journals

British Dental Journal | Journal of Clinical Pediatric Dentistry |

NCBI Bookshelf

Developmental Biology 6th ed. Gilbert, Scott F. Sunderland (MA): Sinauer Associates, Inc.; c2000. Image - Coordinated differentiation and morphogenesis in the mammalian tooth | Tooth Development

Reviews

Seppala M, Zoupa M, Onyekwelu O, Cobourne MT. Tooth development: 1. Generating teeth in the embryo. Dent Update. 2006 Dec;33(10):582-4, 586-8, 590-1.

Tompkins K. Molecular mechanisms of cytodifferentiation in mammalian tooth development. Connect Tissue Res. 2006;47(3):111-8.

Cobourne MT, Sharpe PT. Tooth and jaw: molecular mechanisms of patterning in the first branchial arch. Arch Oral Biol. 2003 Jan;48(1):1-14.

Sharpe PT. Neural crest and tooth morphogenesis. Adv Dent Res. 2001 Aug;15:4-7.

Articles

Lin D, Huang Y, He F, Gu S, Zhang G, Chen Y, Zhang Y. Expression survey of genes critical for tooth development in the human embryonic tooth germ. Dev Dyn. 2007 Mar 29

Nakatomi M, Morita I, Eto K, Ota MS. Sonic hedgehog signaling is important in tooth root development. J Dent Res. 2006 May;85(5):427-31.

Ogawa T, Kapadia H, Feng JQ, Raghow R, Peters H, D'Souza RN. Functional consequences of interactions between Pax9 and Msx1 genes in normal and abnormal tooth development. J Biol Chem. 2006 Jul 7;281(27):18363-9.

Kettunen P, Thesleff I. Expression and function of FGFs-4, -8, and -9 suggest functional redundancy and repetitive use as epithelial signals during tooth morphogenesis. Dev Dyn. 1998 Mar;211(3):256-68.

Books

Note: books are listed for educational and information purposes only and does not suggest a commercial product endorsement.

Search Mar 2007 "tooth development" 4,318 reference articles of which 422 were reviews.

Search PubMed: term = tooth development | odontogenesis | tooth morphogenesis |

Terms

Dental Terms: ameloblast, amelogenin, amine fluoride (AmF), acidulated phosphate fluoride (APF), biomineralization, calcium phosphate (CaP), cementogenesis, dentoenamel junction (DEJ) decayed and filled primary teeth, decayed and filled surfaces on primary teeth, decayed, missing, and filled permanent teeth (DMF), decayed, missing, and filled surfaces on permanent teeth (DMFS), dentin sialophosphoprotein, enamel hypoplasia, ferric aluminum fluoride (FeAlF), periodontal ligament, sodium fluoride (NaF), stannous fluoride (SnF), titanium tetrafluoride (TiF).