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ELife Nov 2023The role of regulated cell death in organ development, particularly the impact of non-apoptotic cell death, remains largely uncharted. Ferroptosis, a non-apoptotic cell...
The role of regulated cell death in organ development, particularly the impact of non-apoptotic cell death, remains largely uncharted. Ferroptosis, a non-apoptotic cell death pathway known for its iron dependence and lethal lipid peroxidation, is currently being rigorously investigated for its pathological functions. The balance between ferroptotic stress (iron and iron-dependent lipid peroxidation) and ferroptosis supervising pathways (anti-lipid peroxidation systems) serves as the key mechanism regulating the activation of ferroptosis. Compared with other forms of regulated necrotic cell death, ferroptosis is critically related to the metabolism of lipid and iron which are also important in organ development. In our study, we examined the role of ferroptosis in organogenesis using an ex vivo tooth germ culture model, investigating the presence and impact of ferroptotic stress on tooth germ development. Our findings revealed that ferroptotic stress increased during tooth development, while the expression of glutathione peroxidase 4 (Gpx4), a crucial anti-lipid peroxidation enzyme, also escalated in dental epithelium/mesenchyme cells. The inhibition of ferroptosis was found to partially rescue erastin-impaired tooth morphogenesis. Our results suggest that while ferroptotic stress is present during tooth organogenesis, its effects are efficaciously controlled by the subsequent upregulation of Gpx4. Notably, an overabundance of ferroptotic stress, as induced by erastin, suppresses tooth morphogenesis.
Topics: Odontogenesis; Organogenesis; Ferroptosis; Lipid Peroxidation; Iron
PubMed: 37991825
DOI: 10.7554/eLife.88745 -
The International Journal of... Feb 1995Extracellular matrix components and cell-derived microstructures are implicated in mineralization processes which occur in dental tissues. The respective role(s) of... (Review)
Review
Extracellular matrix components and cell-derived microstructures are implicated in mineralization processes which occur in dental tissues. The respective role(s) of collagenic and non-collagenic matrix components are reviewed: phosphorylated and non-phosphorylated proteins, proteoglycans and phosphpholipids. Space-filling amphiphilic molecules seem to play an important role in the preorganization and oriented deposition of calcium phosphate on structures serving more or less as passive support in dentine as well as in enamel.
Topics: Amelogenesis; Animals; Dentin; Dentinogenesis; Humans; Microscopy, Electron; Minerals; Odontogenesis; Tooth
PubMed: 7626424
DOI: No ID Found -
Organogenesis Dec 2022The development and repair of dentin are strictly regulated by hundreds of genes. Abnormal dentin development is directly caused by gene mutations and dysregulation....
The development and repair of dentin are strictly regulated by hundreds of genes. Abnormal dentin development is directly caused by gene mutations and dysregulation. Understanding and mastering this signal network is of great significance to the study of tooth development, tissue regeneration, aging, and repair and the treatment of dental diseases. It is necessary to understand the formation and repair mechanism of dentin in order to better treat the dentin lesions caused by various abnormal properties, whether it is to explore the reasons for the formation of dentin defects or to develop clinical drugs to strengthen the method of repairing dentin. Molecular biology of genes related to dentin development and repair are the most important basis for future research.
Topics: Dentin; Dentinogenesis; Odontoblasts; Odontogenesis
PubMed: 35023442
DOI: 10.1080/15476278.2021.2022373 -
The Chinese Journal of Dental Research Jun 2021Wnt signalling pathways have been the focus of intense research activity for decades due to their fundamental role in skeletal and dental development. Wntless, an... (Review)
Review
Wnt signalling pathways have been the focus of intense research activity for decades due to their fundamental role in skeletal and dental development. Wntless, an exclusive chaperone protein for the exocytotis of Wnt ligands, was identified in 2006. In the last decade, the molecular biological studies of Wntless and its genetic studies in human and mice have highlighted the importance of this protein in mineralised tissues, including bone, cartilage and teeth. This article reviews recent developments and discrepancies in the role of Wntless in skeletal and dental development based on mutant phenotypes, as well as the underlying mechanism involved in its molecular and physiological regulation. We conclude that, though some controversial phenotypes exist due to different Cre line resources, Cre recombinase activity and detection time points, Wntless undeniably exerts a context- and stage-dependent regulatory function during the development and homeostasis of both skeletal and dental tissue.
Topics: Animals; Humans; Mice; Odontogenesis; Osteogenesis; Tooth; Wnt Signaling Pathway
PubMed: 34219441
DOI: 10.3290/j.cjdr.b1530533 -
International Journal of Oral Science Nov 2023Tooth root development involves intricate spatiotemporal cellular dynamics and molecular regulation. The initiation of Hertwig's epithelial root sheath (HERS) induces... (Review)
Review
Tooth root development involves intricate spatiotemporal cellular dynamics and molecular regulation. The initiation of Hertwig's epithelial root sheath (HERS) induces odontoblast differentiation and the subsequent radicular dentin deposition. Precisely controlled signaling pathways modulate the behaviors of HERS and the fates of dental mesenchymal stem cells (DMSCs). Disruptions in these pathways lead to defects in root development, such as shortened roots and furcation abnormalities. Advances in dental stem cells, biomaterials, and bioprinting show immense promise for bioengineered tooth root regeneration. However, replicating the developmental intricacies of odontogenesis has not been resolved in clinical treatment and remains a major challenge in this field. Ongoing research focusing on the mechanisms of root development, advanced biomaterials, and manufacturing techniques will enable next-generation biological root regeneration that restores the physiological structure and function of the tooth root. This review summarizes recent discoveries in the underlying mechanisms governing root ontogeny and discusses some recent key findings in developing of new biologically based dental therapies.
Topics: Female; Humans; Tooth Root; Odontogenesis; Epithelial Cells; Cell Differentiation; Biocompatible Materials
PubMed: 38001110
DOI: 10.1038/s41368-023-00258-9 -
Journal of Dental Research Aug 2017Primary cilium is a solitary organelle that emanates from the surface of most postmitotic mammalian cells and serves as a sensory organelle, transmitting the mechanical... (Review)
Review
Primary cilium is a solitary organelle that emanates from the surface of most postmitotic mammalian cells and serves as a sensory organelle, transmitting the mechanical and chemical cues to the cell. Primary cilia are key coordinators of various signaling pathways during development and maintenance of tissue homeostasis. The emerging evidence implicates primary cilia function in tooth development. Primary cilia are located in the dental epithelium and mesenchyme at early stages of tooth development and later during cell differentiation and production of hard tissues. The cilia are present when interactions between both the epithelium and mesenchyme are required for normal morphogenesis. As the primary cilium coordinates several signaling pathways essential for odontogenesis, ciliary defects can interrupt the latter process. Genetic or experimental alterations of cilia function lead to various developmental defects, including supernumerary or missing teeth, enamel and dentin hypoplasia, or teeth crowding. Moreover, dental phenotypes are observed in ciliopathies, including Bardet-Biedl syndrome, Ellis-van Creveld syndrome, Weyers acrofacial dysostosis, cranioectodermal dysplasia, and oral-facial-digital syndrome, altogether demonstrating that primary cilia play a critical role in regulation of both the early odontogenesis and later differentiation of hard tissue-producing cells. Here, we summarize the current evidence for the localization of primary cilia in dental tissues and the impact of disrupted cilia signaling on tooth development in ciliopathies.
Topics: Animals; Cell Differentiation; Cilia; Humans; Maxillofacial Development; Odontogenesis; Signal Transduction
PubMed: 28605602
DOI: 10.1177/0022034517713688 -
Experimental Cell Research Jul 2014Although a big deal of dental research is being focused to the understanding of early stages of tooth development, a huge gap exist on our knowledge on how the dental... (Review)
Review
Although a big deal of dental research is being focused to the understanding of early stages of tooth development, a huge gap exist on our knowledge on how the dental hard tissues are formed and how this process is controlled daily in order to produce very complex and diverse tooth shapes adapted for specific functions. Emerging evidence suggests that clock genes, a family of genes that controls circadian functions within our bodies, regulate also dental mineralized tissues formation. Enamel formation, for example, is subjected to rhythmical molecular signals that occur on short (24h) periods and control the secretion and maturation of the enamel matrix. Accordingly, gene expression and ameloblast functions are also tightly modulated in regular daily intervals. This review summarizes the current knowledge on the circadian controls of dental mineralized tissues development with a special emphasis on amelogenesis.
Topics: Amelogenesis; Animals; Cell Differentiation; Circadian Rhythm; Dental Enamel; Humans; Odontogenesis
PubMed: 24582863
DOI: 10.1016/j.yexcr.2014.02.007 -
Journal of Dental Research Jul 2022Tooth agenesis is a common structural birth defect in humans that results from failure of morphogenesis during early tooth development. The homeobox transcription factor...
Tooth agenesis is a common structural birth defect in humans that results from failure of morphogenesis during early tooth development. The homeobox transcription factor Msx1 and the canonical Wnt signaling pathway are essential for "bud to cap" morphogenesis and are causal factors for tooth agenesis. Our recent study suggested that Msx1 regulates Wnt signaling during early tooth development by suppressing the expression of and in the tooth bud mesenchyme, and it demonstrated partial rescue of -deficient molar teeth by a combination of DKK inhibition and genetic inactivation of SFRPs. In this study, we found that Sostdc1/Wise, another secreted Wnt antagonist, is involved in regulating the odontogenic pathway downstream of Msx1. Whereas expression in the developing tooth germ was not increased in embryos, genetic inactivation of rescued maxillary molar, but not mandibular molar, morphogenesis in mice with full penetrance. Since the ; embryos exhibited ectopic expression in the developing dental mesenchyme, similar to embryos, we generated and analyzed tooth development in ; double and ;; triple mutant mice. The ; double mutants showed rescued maxillary molar morphogenesis at high penetrance, with a small percentage also exhibiting mandibular molars that transitioned to the cap stage. Furthermore, tooth development was rescued in the maxillary and mandibular molars, with full penetrance, in the ;; mice. Together, these data reveal 1) that a key role of Msx1 in driving tooth development through the bud-to-cap transition is to control the expression of and 2) that modulation of Wnt signaling activity by Dkk2 and Sostdc1 plays a crucial role in the Msx1-dependent odontogenic pathway during early tooth morphogenesis.
Topics: Animals; Bone Morphogenetic Protein 4; Gene Expression Regulation, Developmental; MSX1 Transcription Factor; Mesoderm; Mice; Morphogenesis; Odontogenesis; Tooth; Tooth Germ; Wnt Signaling Pathway
PubMed: 35114852
DOI: 10.1177/00220345211070583 -
Current Topics in Developmental Biology 2019Jaw bones and teeth originate from the first pharyngeal arch and develop in closely related ways. Reciprocal epithelial-mesenchymal interactions are required for the... (Review)
Review
Jaw bones and teeth originate from the first pharyngeal arch and develop in closely related ways. Reciprocal epithelial-mesenchymal interactions are required for the early patterning and morphogenesis of both tissues. Here we review the cellular contribution during the development of the jaw bones and teeth. We also highlight signaling networks as well as transcription factors mediating tissue-tissue interactions that are essential for jaw bone and tooth development. Finally, we discuss the potential for stem cell mediated regenerative therapies to mitigate disorders and injuries that affect these organs.
Topics: Animals; Body Patterning; Branchial Region; Humans; Jaw; Odontogenesis; Osteogenesis; Regenerative Medicine
PubMed: 30902260
DOI: 10.1016/bs.ctdb.2018.12.013 -
Wiley Interdisciplinary Reviews.... 2013Teeth are unique to vertebrates and have played a central role in their evolution. The molecular pathways and morphogenetic processes involved in tooth development have... (Review)
Review
Teeth are unique to vertebrates and have played a central role in their evolution. The molecular pathways and morphogenetic processes involved in tooth development have been the focus of intense investigation over the past few decades, and the tooth is an important model system for many areas of research. Developmental biologists have exploited the clear distinction between the epithelium and the underlying mesenchyme during tooth development to elucidate reciprocal epithelial/mesenchymal interactions during organogenesis. The preservation of teeth in the fossil record makes these organs invaluable for the work of paleontologists, anthropologists, and evolutionary biologists. In addition, with the recent identification and characterization of dental stem cells, teeth have become of interest to the field of regenerative medicine. Here, we review the major research areas and studies in the development and evolution of teeth, including morphogenesis, genetics and signaling, evolution of tooth development, and dental stem cells.
Topics: Animals; Biological Evolution; Epithelium; Gene Expression Regulation, Developmental; Mastication; Mesoderm; Metabolic Networks and Pathways; Morphogenesis; Odontogenesis; Stem Cells; Tooth
PubMed: 24009032
DOI: 10.1002/wdev.63