Enhanced BMP signaling results in supernumerary tooth formation in USAG-1 deficient mouse

Murashima-Suginami, Akiko; Takahashi, Kazuyuki; Sakata, Tomoko; Tsukamoto, Hiroko; Sugai, Manabu; Yanagita, Motoko; Shimizu, Akira; Sakurai, Takeshi; Slavkin, Harold C.; Bessho, Kazuhisa

doi:10.1016/j.bbrc.2008.02.135

Cited by 62 publications

(62 citation statements)

References 29 publications

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“…In addition, Dkk1, a potent Wnt signal inhibitor inhibited extra incisor formation in vitro. The BMP antagonist Noggin had a similar inhibitory effect, as also shown recently by Murashima-Suginami et al (Murashima-Suginami et al, 2008) (see Fig. S4 in the supplementary material).…”

Section: Sostdc1 May Not Be the Only Mesenchymal Factor Inhibiting Desupporting

confidence: 86%

“…2). Unlike Murashima-Suginami (Murashima-Suginami, 2007;Murashima-Suginami, 2008), we did not detect marked changes in mesenchymal apoptosis in the Sostdc1-deficient teeth. Taken together, because earlier removal of mesenchyme expressing Sostdc1 causes the development of the extra incisors in the wild-type explants and because this ability is lost with the upregulation of Sostdc1 expression and apoptosis in the epithelium, we suggest that apoptosis may be a relatively downstream event in the in vivo suppression of extra tooth formation.…”

Section: Normal Removal Of Incipient Extra Incisors Involves Epithelicontrasting

confidence: 77%

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Tinkering with the inductive mesenchyme: Sostdc1 uncovers the role of dental mesenchyme in limiting tooth induction

et al. 2009

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Like epithelial organs in general, tooth development involves inductive crosstalk between the epithelium and the mesenchyme. Classically, the inductive potential for tooth formation is considered to reside in the mesenchyme during the visible morphogenesis of teeth, and dental mesenchyme can induce tooth formation even when combined with non-dental epithelium. Here, we have investigated induction of mouse incisors using Sostdc1 (ectodin), a putative antagonist of BMP signaling in the mesenchymal induction of teeth. Deletion of Sostdc1 leads to the full development of single extra incisors adjacent to the main incisors. We show that initially, Sostdc1 expression is limited to the mesenchyme, suggesting that dental mesenchyme may limit supernumerary tooth induction. We test this in wild-type incisors by minimizing the amount of mesenchymal tissue surrounding the incisor tooth germs prior to culture in vitro. The cultured teeth phenocopy the extra incisors phenotype of the Sostdc1-deficient mice. Furthermore, we show that minimizing the amount of dental mesenchyme in cultured Sostdc1-deficient incisors causes the formation of additional de novo incisors that resemble the successional incisor development that results from activated Wnt signaling. Finally, Noggin and Dkk1 prevent individually the formation of extra incisors, and we therefore suggest that inhibition of both BMP and Wnt signaling contributes to the inhibitory role of the dental mesenchyme. Considering the role of mesenchyme in tooth induction and the design of tissue engineering protocols, our work may have uncovered how delicate control of tissue quantities alone influences the outcome between induction and inhibition.

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Section: Sostdc1 May Not Be the Only Mesenchymal Factor Inhibiting Desupporting

confidence: 86%

Section: Normal Removal Of Incipient Extra Incisors Involves Epithelicontrasting

confidence: 77%

Tinkering with the inductive mesenchyme: Sostdc1 uncovers the role of dental mesenchyme in limiting tooth induction

et al. 2009

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“…Mice lacking functional Ectodin have a number of anomalies associated with the mandibular molar dentition, including the presence of a supernumerary molar tooth. Signifi cantly, these mice also have additional incisors in the mandible, [58][59][60] seemingly present due to a failure, in part at least, of normal Ectodin-mediated inhibition from adjacent mesenchyme. 58 Interestingly, Ectodin also has the ability to inhibit WNT signalling and it is likely that correct modulation of this pathway in dental mesencyhme is also an important determinant of tooth number.…”

Section: Bone Morphogenetic Protein Signallingmentioning

confidence: 99%

Revisiting the supernumerary: the epidemiological and molecular basis of extra teeth

et al. 2010

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“…USAG-1-deficient mice showed enlarged enamel knots, markedly altered cusp patterns, extra incisors and molars, and fused molars (Kasai et al 2005;Yanagita et al 2006). The supernumerary maxillary incisor formed as a result of the successive development of the rudimentary upper incisor (Murashima-Suginami et al 2008). Inhibition of BMP signaling rescues supernumerary tooth formation in incisor explants (Murashima-Suginami et al 2008).…”

Section: Tooth Developmentmentioning

confidence: 99%

“…The supernumerary maxillary incisor formed as a result of the successive development of the rudimentary upper incisor (Murashima-Suginami et al 2008). Inhibition of BMP signaling rescues supernumerary tooth formation in incisor explants (Murashima-Suginami et al 2008). These findings indicate that both positive and negative type regulators of BMP signaling control normal tooth development (Fig.…”

Section: Tooth Developmentmentioning

confidence: 99%

Bone Morphogenetic Proteins

Katagiri¹,

Watabe²

2016

Cold Spring Harb Perspect Biol

373

342

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Bone morphogenetic proteins (BMPs), originally identified as osteoinductive components in extracts derived from bone, are now known to play important roles in a wide array of processes during formation and maintenance of various organs including bone, cartilage, muscle, kidney, and blood vessels. BMPs and the related "growth and differentiation factors" (GDFs) are members of the transforming growth factor b (TGF-b) family, and transduce their signals through type I and type II serine -threonine kinase receptors and their intracellular downstream effectors, including Smad proteins. Furthermore, BMP signals are finely tuned by various agonists and antagonists. Because deregulation of the BMP activity at multiple steps in signal transduction is linked to a wide variety of human diseases, therapeutic use of activators and inhibitors of BMP signaling will provide potential avenues for the treatment of the human disorders that are caused by hypo-and hyperactivation of BMP signals, respectively.

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Enhanced BMP signaling results in supernumerary tooth formation in USAG-1 deficient mouse

Cited by 62 publications

References 29 publications

Tinkering with the inductive mesenchyme: Sostdc1 uncovers the role of dental mesenchyme in limiting tooth induction

Tinkering with the inductive mesenchyme: Sostdc1 uncovers the role of dental mesenchyme in limiting tooth induction

Revisiting the supernumerary: the epidemiological and molecular basis of extra teeth

Bone Morphogenetic Proteins

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