scholarly journals USP34 regulates tooth root morphogenesis by stabilizing NFIC

2021 ◽  
Vol 13 (1) ◽  
Author(s):  
Shuang Jiang ◽  
Rui Sheng ◽  
Xingying Qi ◽  
Jun Wang ◽  
Yuchen Guo ◽  
...  
Keyword(s):  
Tooth Development ◽  
Tooth Root ◽  
Short Root ◽  
Physiological Processes ◽  
Root Sheath ◽  
Specific Protease ◽  
Nuclear Factor I ◽  
Root Morphogenesis ◽  
Dependent Protein ◽  
Pulp Cells

AbstractTooth root morphogenesis involves two biological processes, root elongation and dentinogenesis, which are guaranteed by downgrowth of Hertwig’s epithelial root sheath (HERS) and normal odontoblast differentiation. Ubiquitin-dependent protein degradation has been reported to precisely regulate various physiological processes, while its role in tooth development is still elusive. Here we show ubiquitin-specific protease 34 (USP34) plays a pivotal role in root formation. Deletion of Usp34 in dental mesenchymal cells leads to short root anomaly, characterized by truncated roots and thin root dentin. The USP34-deficient dental pulp cells (DPCs) exhibit decreased odontogenic differentiation with downregulation of nuclear factor I/C (NFIC). Overexpression of NFIC partially restores the impaired odontogenic potential of DPCs. These findings indicate that USP34-dependent deubiquitination is critical for root morphogenesis by stabilizing NFIC.

scholarly journals Epithelial Bone Morphogenic Protein 2 and 4 Are Indispensable for Tooth Development

2021 ◽  
Vol 12 ◽  
Author(s):  
Haibin Mu ◽  
Xin Liu ◽  
Shuoshuo Geng ◽  
Dian Su ◽  
Heran Chang ◽  
...  
Keyword(s):  
Cell Death ◽  
Cellular Differentiation ◽  
Tooth Development ◽  
Erk Signaling ◽  
Tooth Root ◽  
Short Root ◽  
Root Sheath ◽  
Bone Morphogenic Protein 2 ◽  
Low Dosage

The Bmp2 and Bmp4 expressed in root mesenchyme were essential for the patterning and cellular differentiation of tooth root. The role of the epithelium-derived Bmps in tooth root development, however, had not been reported. In this study, we found that the double abrogation of Bmp2 and Bmp4 from mouse epithelium caused short root anomaly (SRA). The K14-cre;Bmp2f/f;Bmp4f/f mice exhibited a persistent Hertwig’s Epithelial Root Sheath (HERS) with the reduced cell death, and the down-regulated BMP-Smad4 and Erk signaling pathways. Moreover, the Shh expression in the HERS, the Shh-Gli1 signaling, and Nfic expression in the root mesenchyme of the K14-cre;Bmp2f/f;Bmp4f/f mice were also decreased, indicating a disrupted epithelium- mesenchyme interaction between HERS and root mesenchyme. Such disruption suppressed the Osx and Dspp expression in the root mesenchyme, indicating an impairment on the differentiation and maturation of root odontoblasts. The impaired differentiation and maturation of root odontoblasts could be rescued partially by transgenic Dspp. Therefore, although required in a low dosage and with a functional redundancy, the epithelial Bmp2 and Bmp4 were indispensable for the HERS degeneration, as well as the differentiation and maturation of root mesenchyme.

scholarly journals Essential Role for NFI-C/CTF Transcription-Replication Factor in Tooth Root Development

2003 ◽  
Vol 23 (3) ◽  
pp. 1075-1084 ◽  
Author(s):  
George Steele-Perkins ◽  
Kenneth G. Butz ◽  
Gary E. Lyons ◽  
Margarita Zeichner-David ◽  
Heung-Joong Kim ◽  
...  
Keyword(s):  
Root Development ◽  
Tooth Development ◽  
Physiological Role ◽  
Premature Death ◽  
Tooth Root ◽  
Replication Proteins ◽  
Wild Type ◽  
Organ Systems ◽  
Genes Encoding ◽  
Nuclear Factor I

ABSTRACT The mammalian tooth forms by a series of reciprocal epithelial-mesenchymal interactions. Although several signaling pathways and transcription factors have been implicated in regulating molar crown development, relatively little is known about the regulation of root development. Four genes encoding nuclear factor I (NFI) transcription-replication proteins are present in the mouse genome: Nfia, Nfib, Nfic, and Nfix. In order to elucidate its physiological role(s), we disrupted the Nfic gene in mice. Heterozygous animals appear normal, whereas Nfic−/− mice have unique tooth pathologies: molars lacking roots, thin and brittle mandibular incisors, and weakened abnormal maxillary incisors. Feeding in Nfic−/− mice is impaired, resulting in severe runting and premature death of mice reared on standard laboratory chow. However, a soft-dough diet mitigates the feeding impairment and maintains viability. Although Nfic is expressed in many organ systems, including the developing tooth, the tooth root development defects were the prominent phenotype. Indeed, molar crown development is normal, and well-nourished Nfic−/− animals are fertile and can live as long as their wild-type littermates. The Nfic mutation is the first mutation described that affects primarily tooth root formation and should greatly aid our understanding of postnatal tooth development.

scholarly journals Signaling Pathways Critical for Tooth Root Formation

2017 ◽  
Vol 96 (11) ◽  
pp. 1221-1228 ◽  
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.

scholarly journals The human EDAR 370V/A polymorphism affects tooth root morphology potentially through the modification of a reaction–diffusion system

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Keiichi Kataoka ◽  
Hironori Fujita ◽  
Mutsumi Isa ◽  
Shimpei Gotoh ◽  
Akira Arasaki ◽  
...  
Keyword(s):  
Molecular Mechanisms ◽  
Computational Study ◽  
Reaction Diffusion ◽  
Human Migration ◽  
Reaction Diffusion System ◽  
Diffusion System ◽  
Tooth Root ◽  
Computed Tomography Images ◽  
Diffusion Dynamics ◽  
Root Morphogenesis

AbstractMorphological variations in human teeth have long been recognized and, in particular, the spatial and temporal distribution of two patterns of dental features in Asia, i.e., Sinodonty and Sundadonty, have contributed to our understanding of the human migration history. However, the molecular mechanisms underlying such dental variations have not yet been completely elucidated. Recent studies have clarified that a nonsynonymous variant in the ectodysplasin A receptor gene (EDAR370V/A; rs3827760) contributes to crown traits related to Sinodonty. In this study, we examined the association between theEDARpolymorphism and tooth root traits by using computed tomography images and identified that the effects of theEDARvariant on the number and shape of roots differed depending on the tooth type. In addition, to better understand tooth root morphogenesis, a computational analysis for patterns of tooth roots was performed, assuming a reaction–diffusion system. The computational study suggested that the complicated effects of theEDARpolymorphism could be explained when it is considered that EDAR modifies the syntheses of multiple related molecules working in the reaction–diffusion dynamics. In this study, we shed light on the molecular mechanisms of tooth root morphogenesis, which are less understood in comparison to those of tooth crown morphogenesis.

A Selectable Biomarker in Hair Follicle Cycles – Cathepsins: A Preliminary Study in Murine

2021 ◽  
pp. 1-7
Author(s):  
Jingzhu Bai ◽  
Zijian Gong ◽  
Qingfang Xu ◽  
Haiyan Chen ◽  
Qiaoping Chen ◽  
...  
Keyword(s):  
Hair Follicle ◽  
Hair Cycle ◽  
Biological Factors ◽  
Outer Root Sheath ◽  
Physiological Processes ◽  
Intervention Measures ◽  
Root Sheath ◽  
Inner Root Sheath ◽  
Preliminary Study ◽  
Paraffin Method

<b><i>Background/Objective:</i></b> Hair cycle is regulated by many biological factors. Cathepsins are involved in various physiological processes in human skin. Here, we investigated the cathepsin expression and distribution changes in follicular growth cycles for better understanding the hair cycles and to explore new intervention measures. <b><i>Methods:</i></b> The 24 mice (C57BL/6, female, 7-week old) were selected and removed the back hair via rosin/paraffin method. At Day 8, Day 20, and Day 25, biopsy on post-plucking area was done. Immunohistochemical staining, Western blot, and Q-PCR were used to test the cathepsin B/D/L/E. <b><i>Results:</i></b> In anagen, cathepsins (B, D, L, and E) were distributed in the hair follicle matrix, inner hair root sheath, and hair. In catagen, cathepsins were mainly observed in un-apoptosis inner root sheath and outer root sheath. Expression of cathepsins B-mRNA and L-mRNA was decreased from anagen and catagen to telogen. Cathepsin D-mRNA was increased in catagen and then decreased in telogen. Cathepsin E-mRNA was decreased in catagen and slightly increased in telogen. <b><i>Conclusions:</i></b> The distribution and expression of cathepsins B, D, L, and E in hair follicle changed with hair growth process which indicated that cathepsins might act as selectable biomarkers of hair cycle in different stages.

scholarly journals Contribution of Mesenchymal Proliferation in Tooth Root Morphogenesis

2013 ◽  
Vol 93 (1) ◽  
pp. 78-83 ◽  
Author(s):  
W.-J. Sohn ◽  
M.-A. Choi ◽  
H. Yamamoto ◽  
S. Lee ◽  
Y. Lee ◽  
...  
Keyword(s):  
Tooth Root ◽  
Root Morphogenesis

Immortalized Hertwig's epithelial root sheath cell line works as model for epithelial–mesenchymal interaction during tooth root formation

2019 ◽  
Vol 235 (3) ◽  
pp. 2698-2709 ◽  
Author(s):  
Sicheng Zhang ◽  
Xuebing Li ◽  
Shikai Wang ◽  
Yan Yang ◽  
Weihua Guo ◽  
...  
Keyword(s):  
Cell Line ◽  
Root Formation ◽  
Tooth Root ◽  
Sheath Cell ◽  
Hertwig’S Epithelial Root Sheath ◽  
Root Sheath

scholarly journals The Impact of the Eda Pathway on Tooth Root Development

2017 ◽  
Vol 96 (11) ◽  
pp. 1290-1297 ◽  
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.

The location and characteristics of two populations of dental pulp cells affect tooth development

2009 ◽  
Vol 117 (2) ◽  
pp. 113-121 ◽  
Author(s):  
Yoshinori Sumita ◽  
Shuhei Tsuchiya ◽  
Izumi Asahina ◽  
Hideaki Kagami ◽  
Masaki J. Honda
Keyword(s):  
Dental Pulp ◽  
Tooth Development ◽  
Dental Pulp Cells ◽  
Pulp Cells ◽  
Two Populations

Developmental Properties of the Hertwig’s Epithelial Root Sheath in Mice

2004 ◽  
Vol 83 (9) ◽  
pp. 688-692 ◽  
Author(s):  
H. Yamamoto ◽  
S.-W. Cho ◽  
E.-J. Kim ◽  
J.-Y. Kim ◽  
N. Fujiwara ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Culture System ◽  
Root Formation ◽  
Expression Patterns ◽  
Tooth Root ◽  
Comprehensive Model ◽  
Hertwig’S Epithelial Root Sheath ◽  
Root Sheath ◽  
In Vitro Culture System

Hertwig’s epithelial root sheath (HERS) plays an important role in tooth root formation. In this study, we examined root formation of the first molar in mice, focusing on cell proliferation, cell death, cell migration, and the expression patterns of the signaling molecules, including glycoproteins and proteoglycans between PN8 and PN26. The number of HERS cells decreased during root formation, although HERS retained total length until PN15. The migration of HERS cells did not occur during root formation. Moreover, the immunopositive reaction of laminin beta-3 and syndecan-1 in HERS indicates that both cell adhesion and cell proliferation are essential for HERS development. Bmp-2, Bmp-4, and Msx-2 were expressed in HERS cells during root formation. We also developed an in vitro culture system for investigating the periodontium and suggest that this system provides an excellent vehicle for full exploration, and hence improved understanding, of the development and regeneration of the periodontium. Together, our results provide a comprehensive model describing the morphogenesis of early root development in vertebrates.

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