Ras Signaling Regulates Stem Cells and Amelogenesis in the Mouse Incisor

Zheng, Xu; Goodwin, Alice F.; Tian, Hua; Jheon, Andrew H.; Klein, Ophir D.

doi:10.1177/0022034517717255

Cited by 13 publications

(5 citation statements)

References 29 publications

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“…Ras signaling is activated after FGFs bind to receptor tyrosine kinases (RTKs) and then regulate the proliferative activity of DESCs through the mitogen-activated protein kinase (MAPK) and phosphatidylinositol 3-kinase (PI3K) pathways. Further evidence about the role of MAPK and PI3K in amelogenesis has been proposed through a mouse incisor model of Ras dysregulation[ 57 ].…”

Section: Regulatory Network Of Descs In Mouse Incisorsmentioning

confidence: 99%

New insight into dental epithelial stem cells: Identification, regulation, and function in tooth homeostasis and repair

Gan

Liu

Cui

et al. 2020

WJSC

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Tooth enamel, a highly mineralized tissue covering the outermost area of teeth, is always damaged by dental caries or trauma. Tooth enamel rarely repairs or renews itself, due to the loss of ameloblasts and dental epithelial stem cells (DESCs) once the tooth erupts. Unlike human teeth, mouse incisors grow continuously due to the presence of DESCs that generate enamel-producing ameloblasts and other supporting dental epithelial lineages. The ready accessibility of mouse DESCs and wide availability of related transgenic mouse lines make mouse incisors an excellent model to examine the identity and heterogeneity of dental epithelial stem/progenitor cells; explore the regulatory mechanisms underlying enamel formation; and help answer the open question regarding the therapeutic development of enamel engineering. In the present review, we update the current understanding about the identification of DESCs in mouse incisors and summarize the regulatory mechanisms of enamel formation driven by DESCs. The roles of DESCs during homeostasis and repair are also discussed, which should improve our knowledge regarding enamel tissue engineering.

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Section: Regulatory Network Of Descs In Mouse Incisorsmentioning

confidence: 99%

New insight into dental epithelial stem cells: Identification, regulation, and function in tooth homeostasis and repair

Gan

Liu

Cui

et al. 2020

WJSC

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“…This ectopic expression presents clear evidence for cell fate conversion and should contribute to the establishment of stem and progenitor cell compartments in the extra incisor crown (Sun et al 2016). Activation of mitogen-activated protein kinase (MAPK) cascade associated with ERK and the p38 kinases plays an important role in incisor formation and differentiation (Lee et al 2009; Greenblatt et al 2015; Zheng et al 2017). We found the ectopic presence of pERK and pP38 kinases in the region overlapping with Sox2 + cells in the lingual OEE (Fig.…”

Section: Resultsmentioning

confidence: 99%

Activated Epithelial FGF8 Signaling Induces Fused Supernumerary Incisors

Lin

et al. 2021

J Dent Res

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FGF8, which is specifically expressed in the dental epithelium prior to the E12.5 bud stage, is a key player during odontogenesis, being responsible for the initiation of tooth development. Here, to investigate the impact of persistent FGF8 signaling on tooth development, we forcibly activated FGF8 signaling in the dental epithelium after the bud stage by generating K14-Cre;R26R-Fg8 mice. We found that a unique type of fused supernumerary incisors is formed, although morphologically resembling the features of type II dens invaginatus in humans. Further analysis revealed that ectopically activated epithelial FGF8 alters the cell fate of the incisor lingual outer enamel epithelium, endowing it with odontogenic potential by the activation of several key tooth genes, including Pitx2, Sox2, Lef-1, p38, and Erk1/2, and induces de novo formation of an extra incisor crown lingually in parallel to the original one, leading to the formation of an extra incisor crown and fused with the original incisor eventually. Meanwhile, the overdosed epithelial FGF8 signaling dramatically downregulates the expression of mesenchymal Bmp4, leading to severely impaired enamel mineralization. Based on the location of the extra incisors, we propose that they are likely to be rescued replacement teeth. Our results further demonstrate the essential role of FGF8 signaling for tooth initiation and the establishment of progenitor cells of dental epithelial stem cells during development.

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“…This highlights the importance of cross-talk between the TGFβ, Wnt and FGF signaling pathways in regulating dental epithelium-mesenchyme interactions (Yang et al, 2014). It has also been shown that FGFs bind to receptor tyrosine kinases (RTKs) to activate Ras signaling, which signals through the MAPK and PI3K pathways to regulate epithelial stem cell maintenance and ameloblast differentiation in the adult mouse incisor (Zheng et al, 2017).…”

Section: The Regulation Of Dental Stem Cells During Tissue Homeostasis and Repairmentioning

confidence: 96%

Molecular and cellular mechanisms of tooth development, homeostasis and repair

2020

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The tooth provides an excellent system for deciphering the molecular mechanisms of organogenesis, and has thus been of longstanding interest to developmental and stem cell biologists studying embryonic morphogenesis and adult tissue renewal. In recent years, analyses of molecular signaling networks, together with new insights into cellular heterogeneity, have greatly improved our knowledge of the dynamic epithelial-mesenchymal interactions that take place during tooth development and homeostasis. Here, we review recent progress in the field of mammalian tooth morphogenesis and also discuss the mechanisms regulating stem cell-based dental tissue homeostasis, regeneration and repair. These exciting findings help to lay a foundation that will ultimately enable the application of fundamental research discoveries toward therapies to improve oral health.

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Ras Signaling Regulates Stem Cells and Amelogenesis in the Mouse Incisor

Cited by 13 publications

References 29 publications

New insight into dental epithelial stem cells: Identification, regulation, and function in tooth homeostasis and repair

New insight into dental epithelial stem cells: Identification, regulation, and function in tooth homeostasis and repair

Activated Epithelial FGF8 Signaling Induces Fused Supernumerary Incisors

Molecular and cellular mechanisms of tooth development, homeostasis and repair

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