Role of WNT10A
 in failure of tooth development in humans and zebrafish

Dlx2, a member of the distal-less gene family, is expressed in the first branchial arch, prior to the initiation of tooth development, in distinct, non-overlapping domains in the mesenchyme and the epithelium. In the mesenchyme Dlx2 is expressed proximally, whereas in oral epithelium it is expressed distally. Dlx2 has been shown to be involved in the patterning of the murine dentition, since loss of function of Dlx1 and Dlx2 results in early failure of development of upper molar teeth. We have investigated the regulation of Dlx2 expression to determine how the early epithelial and mesenchymal expression boundaries are maintained, to help to understand the role of these distinct expression domains in patterning of the dentition. Transgenic mice produced with a lacZ reporter construct, containing 3.8 kb upstream sequence of Dlx2, led to the mapping of regulatory regions driving epithelial but not mesenchymal expression in the first branchial arch. We show that the epithelial expression of Dlx2 is regulated by planar signalling by BMP4, which is coexpressed in distal oral epithelium. Mesenchymal expression is regulated by a different mechanism involving FGF8, which is expressed in the overlying epithelium. FGF8 also inhibits expression of Dlx2 in the epithelium by a signalling pathway that requires the mesenchyme. Thus, the signalling molecules BMP4 and FGF8 provide the mechanism for maintaining the strict epithelial and mesenchymal expression domains of Dlx2 in the first arch.

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Emerging Role of Extracellular Vesicles in Bone Remodeling

Journal of Dental Research ◽

10.1177/0022034518764411 ◽

2018 ◽

Vol 97 (8) ◽

pp. 859-868 ◽

Cited By ~ 28

Author(s):

M. Liu ◽

Y. Sun ◽

Q. Zhang

Keyword(s):

Bone Remodeling ◽

Extracellular Vesicles ◽

Transforming Growth Factor ◽

Tooth Development ◽

Osteoclast Differentiation ◽

Nuclear Factor Κb ◽

Transforming Growth Factor Β1 ◽

Bone Diseases ◽

Bioactive Molecules

Extracellular vesicles (EVs), as nanometer-scale particles, include exosomes, microvesicles, and apoptotic bodies. EVs are released by most cell types, such as bone marrow stem cells, osteoblasts, osteoclasts, and immune cells. In bone-remodeling microenvironments, EVs deliver specific proteins (e.g., tenascin C and Sema4D), microRNAs (e.g., miR-214-3p, miR-183-5p, and miR-196a), and other growth factors (e.g., bone morphogenetic protein 1 to 7 and transforming growth factor β1) to osteoblasts and regulate bone formation. In addition, EVs can deliver cytokines, such as RANK (receptor activator of nuclear factor κB) and RANKL (RANK ligand), and microRNAs, such as miR-218 and miR-148a, to modulate osteoclast differentiation during bone resorption. EVs also transfer bioactive molecules and have targeted therapies in bone-related diseases. Moreover, bioactive molecules in EVs are biomarkers in bone-related diseases. We highlight the emerging role of EVs in bone remodeling during physiologic and pathologic conditions and summarize the role of EVs in tooth development and regeneration. At the end of this review, we discuss the challenges of EV application in the treatment of bone diseases.

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The role of the stratum intermedium in tooth development

Oral Surgery Oral Medicine Oral Pathology ◽

10.1016/0030-4220(57)90171-8 ◽

1957 ◽

Vol 10 (4) ◽

pp. 437-443 ◽

Cited By ~ 8

Author(s):

Percy L. Johnson ◽

G. Bevelander

Keyword(s):

Tooth Development

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The Dental Lamina: An Essential Structure for Perpetual Tooth Regeneration in Sharks

Integrative and Comparative Biology ◽

10.1093/icb/icaa102 ◽

2020 ◽

Vol 60 (3) ◽

pp. 644-655

Author(s):

Gareth J Fraser ◽

Ariane Standing ◽

Charlie Underwood ◽

Alexandre P Thiery

Keyword(s):

Murine Model ◽

Tooth Development ◽

Tooth Regeneration ◽

Regenerative Processes ◽

Dental Lamina ◽

Developmental Models ◽

Nonclassical Models ◽

Developmental Shift ◽

Evolutionary Context

Synopsis In recent years, nonclassical models have emerged as mainstays for studies of evolutionary, developmental, and regenerative biology. Genomic advances have promoted the use of alternative taxa for the study of developmental biology, and the shark is one such emerging model vertebrate. Our research utilizes the embryonic shark (Scyliorhinus canicula) to characterize key developmental and regenerative processes that have been overlooked or not possible to study with more classic developmental models. Tooth development is a major event in the construction of the vertebrate body plan, linked in part with the emergence of jaws. Early development of the teeth and morphogenesis is well known from the murine model, but the process of tooth redevelopment and regeneration is less well known. Here we explore the role of the dental lamina in the development of a highly regenerative dentition in sharks. The shark represents a polyphyodont vertebrate with continuously repeated whole tooth regeneration. This is presented as a major developmental shift from the more derived renewal process that the murine model offers, where incisors exhibit continuous renewal and growth of the same tooth. Not only does the shark offer a study system for whole unit dental regeneration, it also represents an important model for understanding the evolutionary context of vertebrate tooth regeneration.

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The Role of PITX2 in Tooth Development

The Molecular Mechanisms of Axenfeld-Rieger Syndrome - Medical Intelligence Unit ◽

10.1007/0-387-28672-1_8 ◽

2007 ◽

pp. 81-92

Author(s):

Brad A. Amendt

Keyword(s):

Tooth Development

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Signaling Pathways Critical for Tooth Root Formation

Journal of Dental Research ◽

10.1177/0022034517717478 ◽

2017 ◽

Vol 96 (11) ◽

pp. 1221-1228 ◽

Cited By ~ 25

Author(s):

J. Wang ◽

J.Q. Feng

Keyword(s):

Signaling Pathways ◽

Root Formation ◽

Root Resorption ◽

Tooth Development ◽

Critical Role ◽

Future Research ◽

Tooth Root ◽

Short Root ◽

Dentin Formation

Tooth is made of an enamel-covered crown and a cementum-covered root. Studies on crown dentin formation have been a major focus in tooth development for several decades. Interestingly, the population prevalence for genetic short root anomaly (SRA) with no apparent defects in crown is close to 1.3%. Furthermore, people with SRA itself are predisposed to root resorption during orthodontic treatment. The discovery of the unique role of Nfic (nuclear factor I C; a transcriptional factor) in controlling root but not crown dentin formation points to a new concept: tooth crown and root have different control mechanisms. Further genetic mechanism studies have identified more key molecules (including Osterix, β-catenin, and sonic hedgehog) that play a critical role in root formation. Extensive studies have also revealed the critical role of Hertwig’s epithelial root sheath in tooth root formation. In addition, Wnt10a has recently been found to be linked to multirooted tooth furcation formation. These exciting findings not only fill the critical gaps in our understanding about tooth root formation but will aid future research regarding the identifying factors controlling tooth root size and the generation of a whole “bio-tooth” for therapeutic purposes. This review starts with human SRA and mainly focuses on recent progress on the roles of NFIC-dependent and NFIC-independent signaling pathways in tooth root formation. Finally, this review includes a list of the various Cre transgenic mouse lines used to achieve tooth root formation–related gene deletion or overexpression, as well as strengths and limitations of each line.

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Tricho-Rhino-Phalangeal Syndrome with Supernumerary Teeth

Journal of Dental Research ◽

10.1177/154405910808701102 ◽

2008 ◽

Vol 87 (11) ◽

pp. 1027-1031 ◽

Cited By ~ 25

Author(s):

P. Kantaputra ◽

I. Miletich ◽

H.-J. Lüdecke ◽

E.Y. Suzuki ◽

V. Praphanphoj ◽

...

Keyword(s):

Transcription Factor ◽

Amino Acid ◽

Zinc Finger ◽

Clinical Features ◽

Tooth Development ◽

Supernumerary Teeth ◽

Gene Encoding ◽

Gata Transcription Factor ◽

Craniofacial Defects

Tricho-rhino-phalangeal syndromes (TRPS) are caused by mutation or deletion of TRPS1, a gene encoding a GATA transcription factor. These disorders are characterized by abnormalities of the hair, face, and selected bones. Rare cases of individuals with TRPS displaying supernumerary teeth have been reported, but none of these has been examined molecularly. We used two different approaches to investigate a possible role of TRPS1 during tooth development. We looked at the expression of Tprs1 during mouse tooth development and analyzed the craniofacial defects of Trps1 mutant mice. In parallel, we investigated whether a 17-year-old Thai boy with clinical features of TRPS and 5 supernumerary teeth had mutation in TRPS1. We report here that Trps1 is expressed during mouse tooth development, and that an individual with TRPS with supernumerary teeth has the amino acid substitution A919V in the GATA zinc finger of TRPS1. These results suggest a role for TRPS1 in tooth morphogenesis.

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The Impact of the Eda Pathway on Tooth Root Development

Journal of Dental Research ◽

10.1177/0022034517725692 ◽

2017 ◽

Vol 96 (11) ◽

pp. 1290-1297 ◽

Cited By ~ 7

Author(s):

J.M. Fons Romero ◽

H. Star ◽

R. Lav ◽

S. Watkins ◽

M. Harrison ◽

...

Keyword(s):

Root Development ◽

Tooth Development ◽

Mouse Development ◽

Direct Role ◽

Root Sheath ◽

Crown Shape ◽

High Incidence ◽

Tooth Number ◽

The Impact

The Eda pathway ( Eda, Edar, Edaradd) plays an important role in tooth development, determining tooth number, crown shape, and enamel formation. Here we show that the Eda pathway also plays a key role in root development. Edar (the receptor) is expressed in Hertwig’s epithelial root sheath (HERS) during root development, with mutant mice showing a high incidence of taurodontism: large pulp chambers lacking or showing delayed bifurcation or trifurcation of the roots. The mouse upper second molars in the Eda pathway mutants show the highest incidence of taurodontism, this enhanced susceptibility being matched in human patients with mutations in EDA-A1. These taurodont teeth form due to defects in the direction of extension of the HERS from the crown, associated with a more extensive area of proliferation of the neighboring root mesenchyme. In those teeth where the angle at which the HERS extends from the crown is very wide and therefore more vertical, the mutant HERSs fail to reach toward the center of the tooth in the normal furcation region, and taurodont teeth are created. The phenotype is variable, however, with milder changes in angle and proliferation leading to normal or delayed furcation. This is the first analysis of the role of Eda in the root, showing a direct role for this pathway during postnatal mouse development, and it suggests that changes in proliferation and angle of HERS may underlie taurodontism in a range of syndromes.

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TGF-β1 Inhibits TLR-mediated Odontoblast Responses to Oral Bacteria

Journal of Dental Research ◽

10.1177/0022034509334846 ◽

2009 ◽

Vol 88 (4) ◽

pp. 333-338 ◽

Cited By ~ 37

Author(s):

O.V. Horst ◽

K.A. Tompkins ◽

S.R. Coats ◽

P.H. Braham ◽

R.P. Darveau ◽

...

Keyword(s):

Cell Surface ◽

Tissue Repair ◽

Lactobacillus Casei ◽

Tooth Development ◽

Fusobacterium Nucleatum ◽

Poor Response ◽

Oral Bacteria ◽

Cellular Processes ◽

Tgf Β1

TGF-β1 exerts diverse functions in tooth development and tissue repair, but its role in microbial defenses of the tooth is not well-understood. Odontoblasts extending their cellular processes into the dentin are the first cells to recognize signals from TGF-β1 and bacteria in carious dentin. This study aimed to determine the role of TGF-β1 in modulating odontoblast responses to oral bacteria. We show that these responses depend upon the expression levels of microbial recognition receptors TLR2 and TLR4 on the cell surface. Porphyromonas gingivalis, Prevotella intermedia, and Fusobacterium nucleatum activated both TLRs, but TLR4 played a greater role. Lack of cell-surface TLR2 was associated with poor response to Streptococcus mutans, Enterococcus faecalis, and Lactobacillus casei. TGF-β1 inhibited TLR2 and TLR4 expression and attenuated odontoblast responses. Our findings suggest that the balance between TLR-mediated inflammation and TGF-β1 anti-inflammatory activity plays an important role in pulpal inflammation.

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