scholarly journals R-Spondin 3 Regulates Mammalian Dental and Craniofacial Development

2021 ◽  
Vol 9 (3) ◽  
pp. 31
Author(s):  
Krishnakali Dasgupta ◽  
Jeffry M. Cesario ◽  
Sara Ha ◽  
Kesava Asam ◽  
Lindsay J. Deacon ◽  
...  
Keyword(s):  
Wnt Signaling ◽  
Tooth Development ◽  
Early Stage ◽  
Craniofacial Development ◽  
Mild Phenotype ◽  
Orofacial Region ◽  
Important Regulator ◽  
Canonical Wnt ◽  
Complex Signaling ◽  
Signaling Interactions

Development of the teeth requires complex signaling interactions between the mesenchyme and the epithelium mediated by multiple pathways. For example, canonical WNT signaling is essential to many aspects of odontogenesis, and inhibiting this pathway blocks tooth development at an early stage. R-spondins (RSPOs) are secreted proteins, and they mostly augment WNT signaling. Although RSPOs have been shown to play important roles in the development of many organs, their role in tooth development is unclear. A previous study reported that mutating Rspo2 in mice led to supernumerary lower molars, while teeth forming at the normal positions showed no significant anomalies. Because multiple Rspo genes are expressed in the orofacial region, it is possible that the relatively mild phenotype of Rspo2 mutants is due to functional compensation by other RSPO proteins. We found that inactivating Rspo3 in the craniofacial mesenchyme caused the loss of lower incisors, which did not progress beyond the bud stage. A simultaneous deletion of Rspo2 and Rspo3 caused severe disruption of craniofacial development from early stages, which was accompanied with impaired development of all teeth. Together, these results indicate that Rspo3 is an important regulator of mammalian dental and craniofacial development.

Wnt Production in Dental Epithelium Is Crucial for Tooth Differentiation

2019 ◽  
Vol 98 (5) ◽  
pp. 580-588 ◽  
Author(s):  
Y. Xiong ◽  
Y. Fang ◽  
Y. Qian ◽  
Y. Liu ◽  
X. Yang ◽  
...  
Keyword(s):  
Wnt Signaling ◽  
Signaling Pathway ◽  
Tooth Development ◽  
Wnt Signaling Pathway ◽  
Conditional Knockout ◽  
Canonical Wnt Signaling ◽  
Odontoblast Differentiation ◽  
Wnt Ligands ◽  
Dental Epithelium ◽  
Canonical Wnt

The Wnt ligands display varied spatiotemporal expression in the epithelium and mesenchyme in the developing tooth. Thus far, the actions of these differentially expressed Wnt ligands on tooth development are not clear. Shh expression specifies the odontogenic epithelium during initiation and is consistently restricted to the dental epithelium during tooth development. In this study, we inactivate Wntless ( Wls), the key regulator for Wnt trafficking, by Shh-Cre to investigate how the Wnt ligands produced in the dental epithelium lineage act on tooth development. We find that conditional knockout of Wls by Shh-Cre leads to defective ameloblast and odontoblast differentiation. WlsShh-Cre teeth display reduced canonical Wnt signaling activity in the inner enamel epithelium and the underlying mesenchyme at the early bell stage, as exhibited by target gene expression and BAT-gal staining. The expression of Wnt5a and Wnt10b is not changed in WlsShh-Cre teeth. By contrast, Wnt10a expression is significantly increased in response to epithelial Wls deficiency. In addition, the expression of Hedgehog signaling pathway components Shh, Gli1, and Patched1 was greatly decreased in WlsShh-Cre teeth. Epithelial Wls loss of function in Shh lineage also leads to aberrant cell proliferation in dental epithelium and mesenchyme at embryonic day 16.5; however, the cell apoptosis is unaffected. Moreover, we find that Decorin and Col1a1, the key markers for odontoblast differentiation that are downregulated in WlsShh-Cre teeth, act as direct downstream targets of the canonical Wnt signaling pathway by chromatin immunoprecipitation analysis. Additionally, Decorin and Col1a1 expression can be increased by lithium chloride (LiCl) treatment in the in vitro tooth explants. Taken together, our results suggest that the spatial expression of Wnt ligands within the dental epithelial lineage regulates the differentiation of tooth structures in later stages.

Developmental Biology II: The Role of WNT Signaling in Bone Regeneration

2019 ◽  
Author(s):  
Mimi R. Borrelli ◽  
Ledibabari M. Ngaage ◽  
Derrick C. Wan ◽  
Michael T. Longaker ◽  
H. Peter Lorenz
Keyword(s):  
Wnt Signaling ◽  
Bone Regeneration ◽  
Bone Development ◽  
Integration Site ◽  
Wnt Signaling Pathway ◽  
Cell Proliferation And Differentiation ◽  
Important Regulator ◽  
Cell Niche ◽  
Canonical Wnt

Wingless-related integration site (Wnt) signaling is an important regulator of bone development and regeneration. Wnts are short-range signaling molecules which act within the skeletal stem cell niche to influence cell proliferation and differentiation. Nineteen different Wnts have been identified in humans. Disruptions to Wnt signaling can lead to impairments in bone healing. Recent work has elucidated the complexities of Wnt signaling during bone development, repair, and regeneration, and highlighted its value as a potential therapeutic target for tissue regeneration. Here, we discuss the role of the canonical-Wnt-signaling pathway, its regulatory role in bone regeneration, and the recent clinical advance made towards its manipulation in regenerative medicine. This review contains 3 figures and 50 references.  Keywords: osteogenesis, bone regeneration, bone remodeling, endochondral ossification, osteoblast, osteoprogenitor, lithium, fracture healing

scholarly journals Synergistic roles of Wnt modulators R-spondin2 and R-spondin3 in craniofacial morphogenesis and dental development

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Nora Alhazmi ◽  
Shannon H. Carroll ◽  
Kenta Kawasaki ◽  
Katherine C. Woronowicz ◽  
Shawn A. Hallett ◽  
...  
Keyword(s):  
Wnt Signaling ◽  
Tooth Development ◽  
Bone Development ◽  
Critical Role ◽  
Tooth Germ ◽  
Craniofacial Development ◽  
Craniofacial Skeleton ◽  
Mouse Development ◽  
Tooth Number ◽  
Fin Development

AbstractWnt signaling plays a critical role in craniofacial patterning, as well as tooth and bone development. Rspo2 and Rspo3 are key regulators of Wnt signaling. However, their coordinated function and relative requirement in craniofacial development and odontogensis are poorly understood. We showed that in zebrafish rspo2 and rspo3 are both expressed in osteoprogenitors in the embryonic craniofacial skeleton. This is in contrast to mouse development, where Rspo3 is expressed in osteoprogenitors while Rspo2 expression is not observed. In zebrafish, rspo2 and rspo3 are broadly expressed in the pulp, odontoblasts and epithelial crypts. However, in the developing molars of the mouse, Rspo3 is largely expressed in the dental follicle and alveolar mesenchyme while Rspo2 expression is restricted to the tooth germ. While Rspo3 ablation in the mouse is embryonic lethal, zebrafish rspo3-/- mutants are viable with modest decrease in Meckel’s cartilage rostral length. However, compound disruption of rspo3 and rspo2 revealed synergistic roles of these genes in cartilage morphogenesis, fin development, and pharyngeal tooth development. Adult rspo3−/− zebrafish mutants exhibit a dysmorphic cranial skeleton and decreased average tooth number. This study highlights the differential functions of Rspo2 and Rspo3 in dentocranial morphogenesis in zebrafish and in mouse.

scholarly journals Visualizing canonical Wnt signaling during mouse craniofacial development

2009 ◽  
pp. NA-NA ◽  
Author(s):  
Preethi Mani ◽  
Andrew Jarrell ◽  
John Myers ◽  
Radhika Atit
Keyword(s):  
Wnt Signaling ◽  
Craniofacial Development ◽  
Canonical Wnt Signaling ◽  
Canonical Wnt

scholarly journals A comprehensive investigation of colorectal cancer progression, from the early to late-stage, a systems biology approach

2020 ◽  
Author(s):  
Mohammad Ghorbani ◽  
Yazdan Asgari
Keyword(s):  
Colorectal Cancer ◽  
Wnt Signaling ◽  
Cancer Progression ◽  
Late Stage ◽  
Early Stage ◽  
Differentially Expressed Gene ◽  
Stage 4 ◽  
Colorectal Cancer Progression ◽  
Stage 1 ◽  
Canonical Wnt

AbstractColorectal cancer is a widespread malignancy with a concerning mortality rate. It could be curable at the first stages, but the progress of the disease and reaching to the stage-4 could make shift the treatments from curative to palliative. In this stage, the survival rate is meager, and therapy options are limited. The question is, what are the hallmarks of this stage and what genes are involved? What mechanism and pathways could drive such a malign shift from stage-1 to stage-4? In this study, first we identified the core modules for both the stage-1 and stage-4 which four of them have a significant role in stage-1 and two of them have a role in stage-4. Then we investigated the gene ontology and hallmarks analysis for each stage. According to the results, the immune-related process, especially interferon-gamma, impacts stage-1 in colorectal cancer. Concerning stage-4, extracellular matrix ontologies, and metastatic hallmarks are in charge. At last, we performed a differentially expressed gene analysis of stage-4 vs. stage-1 and analyzed their pathways which reasonably undergone a hypo/hyperactivity or being abnormally regulated through the cancer progression. We found that lncRNA in canonical WNT signaling and colon cancer has the most significant pathways, followed by WNT signaling, which means that these pathways may be the driver for the development from early-stage to late-stage. Of these lncRNAs, we had two upregulated kind, H19, and HOTAIR, which both can be involved and mediate metastasis and invasion in colorectal cancer.

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