scholarly journals Epiprofin Regulates Enamel Formation and Tooth Morphogenesis by Controlling Epithelial-Mesenchymal Interactions During Tooth Development

2016 ◽  
Vol 32 (3) ◽  
pp. 601-610 ◽  
Author(s):  
Takashi Nakamura ◽  
Lucia Jimenez-Rojo ◽  
Eiki Koyama ◽  
Maurizio Pacifici ◽  
Susana de Vega ◽  
...  
Keyword(s):  
Tooth Development ◽  
Enamel Formation ◽  
Tooth Morphogenesis

scholarly journals Smad7 Regulates Dental Epithelial Proliferation during Tooth Development

2019 ◽  
Vol 98 (12) ◽  
pp. 1376-1385 ◽  
Author(s):  
Z. Liu ◽  
T. Chen ◽  
D. Bai ◽  
W. Tian ◽  
Y. Chen
Keyword(s):  
Cell Cycle ◽  
Cell Proliferation ◽  
Cyclin D1 ◽  
Transforming Growth Factor ◽  
Tooth Development ◽  
Tooth Germ ◽  
Transforming Growth Factor Β ◽  
Tooth Size ◽  
Dental Epithelium ◽  
Tooth Morphogenesis

Tooth morphogenesis involves dynamic changes in shape and size as it proceeds through the bud, cap, and bell stages. This process requires exact regulation of cell proliferation and differentiation. Smad7, a general antagonist against transforming growth factor–β (TGF-β) signaling, is necessary for maintaining homeostasis and proper functionality in many organs. While TGF-β signaling is widely involved in tooth morphogenesis, the precise role of Smad7 in tooth development remains unknown. In this study, we showed that Smad7 is expressed in the developing mouse molars with a high level in the dental epithelium but a moderate to weak level in the dental mesenchyme. Smad7 deficiency led to a profound decrease in tooth size primarily due to a severely compromised cell proliferation capability in the dental epithelium. Consistent with the tooth shrinkage phenotype, RNA sequencing (RNA-seq) analysis revealed that Smad7 ablation downregulated genes referred to epithelial cell proliferation and cell cycle G1/S phase transition, whereas the upregulated genes were involved in responding to TGF-β signaling and cell cycle arrest. Among these genes, the expression of Cdkn1a (encoding p21), a negative cell proliferation regulator, was remarkably elevated in parallel with the diminution of Ccnd1 encoding the crucial cell cycle regulator cyclin D1 in the dental epithelium. Meanwhile, the expression level of p-Smad2/3 was ectopically elevated in the developing tooth germ of Smad7 null mice, indicating the hyperactivation of the canonical TGF-β signaling. These effects were reversed by addition of TGF-β signaling inhibitor in cell cultures of Smad7−/− molar tooth germs, with rescued expression of cyclin D1 and cell proliferation rate. In sum, our studies demonstrate that Smad7 functions primarily as a positive regulator of cell proliferation via inhibition of the canonical TGF-β signaling during dental epithelium development and highlight a crucial role for Smad7 in regulating tooth size.

Epithelial Fibroblast Growth Factor Receptor 1 Regulates Enamel Formation

2008 ◽  
Vol 87 (3) ◽  
pp. 238-243 ◽  
Author(s):  
K. Takamori ◽  
R. Hosokawa ◽  
X. Xu ◽  
X. Deng ◽  
P. Bringas ◽  
...  
Keyword(s):  
Growth Factor ◽  
Fibroblast Growth Factor ◽  
Tooth Development ◽  
Critical Role ◽  
Growth Factor Receptor ◽  
Fibroblast Growth ◽  
Fgf Signaling ◽  
Enamel Formation ◽  
Enamel Structure ◽  
A Cell

The interaction between epithelial and mesenchymal tissues plays a critical role in the development of organs such as teeth, lungs, and hair. During tooth development, fibroblast growth factor (FGF) signaling is critical for regulating reciprocal epithelial and mesenchymal interactions. FGF signaling requires FGF ligands and their receptors (FGFRs). In this study, we investigated the role of epithelial FGF signaling in tooth development, using the Cre-loxp system to create tissue-specific inactivation of Fgfr1 in mice. In K14-Cre;Fgfr1 fl/fl mice, the apical sides of enamel-secreting ameloblasts failed to adhere properly to each other, although ameloblast differentiation was unaffected at early stages. Prior to eruption, enamel structure was compromised in the K14-Cre;Fgfr1 fl/fl mice and displayed severe enamel defects that mimic amelogenesis imperfecta (AI), with a rough, irregular enamel surface. These results suggest that there is a cell-autonomous requirement for FGF signaling in the dental epithelium during enamel formation. Loss of Fgfr1 affects ameloblast organization at the enamel-secretory stage and, hence, the formation of enamel.

Msx1 controls inductive signaling in mammalian tooth morphogenesis

Development ◽  
1996 ◽  
Vol 122 (10) ◽  
pp. 3035-3044 ◽  
Author(s):  
Y. Chen ◽  
M. Bei ◽  
I. Woo ◽  
I. Satokata ◽  
R. Maas
Keyword(s):  
Matrix Protein ◽  
Tooth Development ◽  
Molar Tooth ◽  
Extracellular Matrix Protein ◽  
Msx Genes ◽  
Tooth Morphogenesis ◽  
Tooth Germs ◽  
Vertebrate Organogenesis ◽  
Inductive Signaling

Members of the Msx homeobox family are thought to play important roles in inductive tissue interactions during vertebrate organogenesis, but their precise developmental function has been unclear. Mice deficient for Msx1 exhibit defects in craniofacial development and a failure of tooth morphogenesis, with an arrest in molar tooth development at the E13.5 bud stage. Because of its potential for experimental manipulation, the murine molar tooth germ provides a powerful system for studying the role of Msx genes in inductive signaling during organogenesis. To further analyze the role of Msx1 in regulating epithelial-mesenchymal interactions during tooth morphogenesis, we have examined the expression of several potential Msx1 downstream genes in Msx1 mutant tooth germs and we have performed functional experiments designed to order these genes into a pathway. Our results show that expression of Bone Morphogenetic Protein 4 (BMP4), the HMG box gene Lef1 and the heparan sulfate proteoglycan syndecan-1 is specifically reduced in Msx1 mutant dental mesenchyme, while expression of the extracellular matrix protein tenascin is unaffected. BMP4 soaked beads can induce Bmp4 and Lef1 expression in explanted wild-type dental mesenchymes, but only Lef1 expression in Msx1 mutant dental mesenchyme. We thus conclude that epithelial BMP4 induces its own expression in dental mesenchyme in a manner that requires Msx1. In turn, we show that addition of BMP4 to Msx1 deficient tooth germs bypasses the requirement for Msx1 and rescues epithelial development from the bud stage to the E14.5 cap stage. Lastly, we show that FGFs induce syndecan-1 expression in dental mesenchyme in a manner that also requires Msx-1. These results integrate Msx1 into a regulatory hierarchy in early tooth morphogenesis and demonstrate that Msx1 is not only expressed in dental mesenchyme in response to epithelial signals, but also in turn regulates the reciprocal expression of inductive signals in the mesenchyme which then act back upon the dental epithelium. We propose that Msx genes function repetitively during vertebrate organogenesis to permit inductive signaling to occur back and forth between tissue layers.

scholarly journals Extracellular proteolysis alters tooth development in transgenic mice expressing urokinase-type plasminogen activator in the enamel organ

Development ◽  
1999 ◽  
Vol 126 (5) ◽  
pp. 903-912
Author(s):  
H.M. Zhou ◽  
A. Nichols ◽  
A. Wohlwend ◽  
I. Bolon ◽  
J.D. Vassalli
Keyword(s):  
Transgenic Mice ◽  
Plasminogen Activator ◽  
Transforming Growth Factor ◽  
Tooth Development ◽  
Enamel Organ ◽  
Enamel Formation ◽  
Type Plasminogen Activator ◽  
Urokinase Type Plasminogen Activator ◽  
Enamel Epithelium ◽  
Extracellular Proteolysis

By catalyzing plasmin formation, the urokinase-type plasminogen activator (uPA) can generate widespread extracellular proteolysis and thereby play an important role in physiological and pathological processes. Dysregulated expression of uPA during organogenesis may be a cause of developmental defects. Targeted epithelial expression of a uPA-encoding transgene under the control of the keratin type-5 promoter resulted in enzyme production by the enamel epithelium, which does not normally express uPA, and altered tooth development. The incisors of transgenic mice were fragile, chalky-white and, by scanning electron microscopy, their labial surface appeared granular. This phenotype was attributed to a defect in enamel formation during incisor development, resulting from structural and functional alterations of the ameloblasts that differentiate from the labial enamel epithelium. Immunofluorescence revealed that disorganization of the ameloblast layer was associated with a loss of laminin-5, an extracellular matrix molecule mediating epithelial anchorage. Amelogenin, a key protein in enamel formation, was markedly decreased at the enamel-dentin junction in transgenics, presumably because of an apparent alteration in the polarity of its secretion. In addition, increased levels of active transforming growth factor-beta could be demonstrated in mandibles of transgenic mice. Since the alterations detected could be attributed to uPA catalytic activity, this model provides evidence as to how dysregulated proteolysis, involving uPA or other extracellular proteases, may have developmental consequences such as those leading to enamel defects.

scholarly journals The Prx1 Homeobox Gene is Critical for Molar Tooth Morphogenesis

2006 ◽  
Vol 85 (10) ◽  
pp. 888-893 ◽  
Author(s):  
J.M. Mitchell ◽  
D.M. Hicklin ◽  
P.M. Doughty ◽  
J.H. Hicklin ◽  
J.W. Dickert ◽  
...  
Keyword(s):  
Tooth Development ◽  
Three Dimensional ◽  
Homeobox Gene ◽  
Molar Tooth ◽  
Mandibular Incisor ◽  
Mandibular Hypoplasia ◽  
Morphological Defects ◽  
Mandibular Region ◽  
Tooth Morphogenesis

The paired-related homeobox genes, Prx1 and Prx2, encode transcription factors critical for orofacial development. Prx1−/−/ Prx2−/− neonates have mandibular hypoplasia and malformed mandibular incisors. Although the mandibular incisor phenotype has been briefly described (ten Berge et al., 1998 , 2001 ; Lu et al., 1999 ), very little is known about the role of Prx proteins during tooth morphogenesis. Since the posterior mandibular region was relatively normal, we examined molar tooth development in Prx1−/−/ Prx2−/− embryos to determine whether the tooth malformation is primary to the loss of Prx protein or secondary to defects in surrounding tissues. Three-dimensional (3D) morphological reconstructions demonstrated that Prx1−/−/ Prx2−/− embryos had molar malformations, including cuspal changes and ectopic epithelial projections. Although we demonstrate that Prx1 protein is expressed only mesenchymally, 3D reconstructions showed important morphological defects in epithelial tissues at the cap and bell stages. Analysis of these data suggests that the Prx homeoproteins are critical for mesenchymal-epithelial signaling during tooth morphogenesis.

scholarly journals AESTHETIC SOLUTION TO FLUOROSIS IN A CHILD

2017 ◽  
Vol 26 (1) ◽  
pp. 96
Author(s):  
Juliana Cardoso Neves Do Amaral ◽  
Erika Calvano Küchler ◽  
Lívia Azeredo Alves Antunes ◽  
Leonardo Dos Santos Antunes ◽  
Marcelo De Castro Costa
Keyword(s):  
Minimally Invasive ◽  
Clinical Characteristics ◽  
Tooth Development ◽  
Tooth Enamel ◽  
Dental Fluorosis ◽  
Permanent Teeth ◽  
Enamel Formation ◽  
History Of ◽  
Chronic Ingestion ◽  
Different Sources

Dental fluorosis is a defect of enamel formation caused by chronic ingestion of fluoride from different sources during tooth development, which results in interference in proper mineralization. Clinically the tooth enamel may present as white striae along the lines of enamel, opaque white spot and in more severe cases as brown spots. Diagnosis is based on clinical characteristics associated with a history of exposure to fluoride. The aim of this report is to present a treatment in a child with severe aesthetic compromising in anterior maxillary permanent teeth caused by fluorosis. The treatment was based on a combination of three techniques in order to be minimally invasive, enhance aesthetics and preserving the dental structure.

Enamel Knots as Signaling Centers Linking Tooth Morphogenesis and Odontoblast Differentiation

2001 ◽  
Vol 15 (1) ◽  
pp. 14-18 ◽  
Author(s):  
Irma Thesleff ◽  
Soile Keranen ◽  
Jukka Jernvall
Keyword(s):  
Tooth Development ◽  
Experimental Studies ◽  
Cell Lineage ◽  
Signaling Molecules ◽  
Enamel Knot ◽  
Odontoblast Differentiation ◽  
Dental Papilla ◽  
Dental Epithelium ◽  
Tooth Morphogenesis ◽  
Enamel Knots

Odontoblasts differentiate from the cells of the dental papilla, and it has been well-established that their differentiation in developing teeth is induced by the dental epithelium. In experimental studies, no other mesenchymal cells have been shown to have the capacity to differentiate into odontoblasts, indicating that the dental papilla cells have been committed to odontoblast cell lineage during earlier developmental stages. We propose that the advancing differentiation within the odontoblast cell lineage is regulated by sequential epithelial signals. The first epithelial signals from the early oral ectoderm induce the odontogenic potential in the cranial neural crest cells. The next step in the determination of the odontogenic cell lineage is the development of the dental papilla from odontogenic mesenchyme. The formation of the dental papilla starts at the onset of the transition from the bud to the cap stage of tooth morphogenesis, and this is regulated by epithelial signals from the primary enamel knot. The primary enamel knot is a signaling center which forms at the tip of the epithelial tooth bud. It becomes fully developed and morphologically discernible in the cap-stage dental epithelium and expresses at least ten different signaling molecules belonging to the BMP, FGF, Hh, and Wnt families. In molar teeth, secondary enamel knots appear in the enamel epithelium at the sites of the future cusps. They also express several signaling molecules, and their formation precedes the folding and growth of the epithelium. The differentiation of odontoblasts always starts from the tips of the cusps, and therefore, it is conceivable that some of the signals expressed in the enamel knots may act as inducers of odontoblast differentiation. The functions of the different signals in enamel knots are not precisely known. We have shown that FGFs stimulate the proliferation of mesenchymal as well as epithelial cells, and they may also regulate the growth of the cusps. We have proposed that the enamel knot signals also have important roles, together with mesenchymal signals, in regulating the patterning of the cusps and hence the shape of the tooth crown. We suggest that the enamel knots are central regulators of tooth development, since they link cell differentiation to morphogenesis.

scholarly journals Signaling Modulation by miRNA-221-3p During Tooth Morphogenesis in Mice

2021 ◽  
Vol 9 ◽  
Author(s):  
Yam Prasad Aryal ◽  
Tae-Young Kim ◽  
Eui-Seon Lee ◽  
Chang-Hyeon An ◽  
Ji-Youn Kim ◽  
...  
Keyword(s):  
Cellular Proliferation ◽  
Tooth Development ◽  
Expression Patterns ◽  
Loss Of Function ◽  
Functional Roles ◽  
Cellular Events ◽  
Root Sheath ◽  
Enamel Epithelium ◽  
Tooth Morphogenesis

miRNAs are conserved short non-coding RNAs that play a role in the modulation of various biological pathways during tissue and organ morphogenesis. In this study, the function of miRNA-221-3p in tooth development, through its loss or gain in function was evaluated. A variety of techniques were utilized to evaluate detailed functional roles of miRNA-221-3p during odontogenesis, including in vitro tooth cultivation, renal capsule transplantation, in situ hybridization, real-time PCR, and immunohistochemistry. Two-day in vitro tooth cultivation at E13 identified altered cellular events, including cellular proliferation, apoptosis, adhesion, and cytoskeletal arrangement, with the loss and gain of miRNA-221-3p. qPCR analysis revealed alterations in gene expression of tooth-related signaling molecules, including β-catenin, Bmp2, Bmp4, Fgf4, Ptch1, and Shh, when inhibited with miRNA-221-3p and mimic. Also, the inhibition of miRNA-221-3p demonstrated increased mesenchymal localizations of pSMAD1/5/8, alongside decreased expression patterns of Shh and Fgf4 within inner enamel epithelium (IEE) in E13 + 2 days in vitro cultivated teeth. Moreover, 1-week renal transplantation of in vitro cultivated teeth had smaller tooth size with reduced enamel and dentin matrices, along with increased cellular proliferation and Shh expression along the Hertwig epithelial root sheath (HERS), within the inhibitor group. Similarly, in 3-week renal calcified teeth, the overexpression of miRNA-221-3p did not affect tooth phenotype, while the loss of function resulted in long and slender teeth with short mesiodistal length. This study provides evidence that a suitable level of miRNA-221-3p is required for the modulation of major signaling pathways, including Wnt, Bmp, and Shh, during tooth morphogenesis.

Tooth development in a scincid lizard, Chalcides viridanus (Squamata), with particular attention to enamel formation

2004 ◽  
Vol 319 (1) ◽  
pp. 71-89 ◽  
Author(s):  
Sidney Delgado ◽  
Tiphaine Davit-B�al ◽  
Fran�oise Allizard ◽  
Jean-Yves Sire
Keyword(s):  
Tooth Development ◽  
Enamel Formation

A Rare Case of Congenital Missing Mandibular Second Molar: Report and Review of Literature

2020 ◽  
Author(s):  
Deepashri H Kambalimath
Keyword(s):  
Tooth Development ◽  
Rare Condition ◽  
Review Of Literature ◽  
Indian Literature ◽  
Missing Teeth ◽  
Second Molar ◽  
The World ◽  
Mandibular Second Molar ◽  
Sporadic Cases ◽  
Genetic And Environmental Factors

Congenital missing permanent second molar is an extremely rare condition. Non syndromic mandibular second molar agenesis associated with other anomalies has occasionally been reported in literature, but isolated sporadic cases are rarely observed. Number of interactions between genetic and environmental factors during the process of tooth development might be the causative etiology for agenesis. This report presents an isolated case of hypodontia with absence of bilateral mandibular second molar agenesis in a healthy 18 year old female patient is presented and literature review on prevalence of most missing teeth with incidence of missing second molar in various regions of the world and in various regions of Indian continent is presented. No such case has been reported in Indian literature so far.

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