The Shh signalling pathway in tooth development: defects in Gli2 and Gli3 mutants

Development ◽  
1998 ◽  
Vol 125 (15) ◽  
pp. 2803-2811 ◽  
Author(s):  
Z. Hardcastle ◽  
R. Mo ◽  
C.C. Hui ◽  
P.T. Sharpe
Keyword(s):  
Tooth Development ◽  
Tooth Germ ◽  
Signalling Pathway ◽  
Abnormal Development ◽  
Maxillary Incisor ◽  
Expression Of Genes ◽  
Hedgehog Signalling Pathway ◽  
Tooth Germs ◽  
Sonic Hedgehog Signalling ◽  
Incisor Development

The expression of genes involved in the Sonic Hedgehog signalling pathway, including Shh, Ptc, Smo, Gli1, Gli2 and Gli3, were found to be expressed in temporal and spatial patterns during early murine tooth development, suggestive of a role in early tooth germ initiation and subsequent epithelial-mesenchymal interactions. Of these Ptc, Smo, Gli1, Gli2 and Gli3 were expressed in epithelium and mesenchyme whereas Shh was only detected in epithelium. This suggests that Shh is involved in both lateral (epithelial-mesenchymal) and planar (epithelial-epithelial) signalling in early tooth development. Ectopic application of Shh protein to mandibular mesenchyme induced the expression of Ptc and Gli1. Addition of exogenous Shh protein directly into early tooth germs and adjacent to tooth germs, resulted in abnormal epithelial invagination, indicative of a role for Shh in epithelial cell proliferation. In order to assess the possible role of this pathway, tooth development in Gli2 and Gli3 mutant embryos was investigated. Gli2 mutants were found to have abnormal development of maxillary incisors, probably resulting from a mild holoprosencephaly, whereas Gli3 mutants had no major tooth abnormalities. Gli2/Gli3 double homozygous mutants did not develop any normal teeth and did not survive beyond embryonic day 14.5; however, Gli2(−/−); Gli3(+/−) did survive until birth and had small molars and mandibular incisors whereas maxillary incisor development was arrested as a rudimentary epithelial thickening. These results show an essential role for Shh signalling in tooth development that involves functional redundancy of downstream Gli genes.

scholarly journals BMP Activity Is Required for Tooth Development from the Lamina to Bud Stage

2012 ◽  
Vol 91 (7) ◽  
pp. 690-695 ◽  
Author(s):  
Y. Wang ◽  
L. Li ◽  
Y. Zheng ◽  
G. Yuan ◽  
G. Yang ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Molecular Marker ◽  
Tooth Development ◽  
Tooth Germ ◽  
Bmp Signaling ◽  
Expression Of Genes ◽  
Dental Epithelium ◽  
Initiation Stage ◽  
Transgenic Embryos ◽  
Bmp Antagonist

Several Bmp genes are expressed in the developing mouse tooth germ from the initiation to the late-differentiation stages, and play pivotal roles in multiple steps of tooth development. In this study, we investigated the requirement of BMP activity in early tooth development by transgenic overexpression of the extracellular BMP antagonist Noggin. We show that overexpression of Noggin in the dental epithelium at the tooth initiation stage arrests tooth development at the lamina/early-bud stage. This phenotype is coupled with a significantly reduced level of cell proliferation rate and a down-regulation of Cyclin-D1 expression, specifically in the dental epithelium. Despite unaltered expression of genes known to be implicated in early tooth development in the dental mesenchyme and dental epithelium of transgenic embryos, the expression of Pitx2, a molecular marker for the dental epithelium, became down-regulated, suggesting the loss of odontogenic fate in the transgenic dental epithelium. Our results reveal a novel role for BMP signaling in the progression of tooth development from the lamina stage to the bud stage by regulating cell proliferation and by maintaining odontogenic fate of the dental epithelium.

scholarly journals Expression, localization and synthesis of small leucine-rich proteoglycans in developing mouse molar tooth germ

2020 ◽  
Vol 64 (1) ◽  
Author(s):  
Angammana Randilini ◽  
Kaoru Fujikawa ◽  
Shunichi Shibata
Keyword(s):  
Organ Culture ◽  
Developmental Stages ◽  
Tooth Development ◽  
Expression Patterns ◽  
Tooth Germ ◽  
Molar Tooth ◽  
Cervical Region ◽  
Metabolic Labeling ◽  
Tooth Formation ◽  
Tooth Germs

The gene expression and protein synthesis of small leucine-rich proteoglycans (SLRPs), including decorin, biglycan, fibromodulin, and lumican, was analyzed in the context of the hypothesis that they are closely related to tooth formation. In situ hybridization, immunohistochemistry, and organ culture with metabolic labeling of [35S] were carried out in mouse first molar tooth germs of different developmental stages using ICR mice at embryonic day (E) 13.5 to postnatal day (P) 7.0. At the bud and cap stage, decorin mRNA was expressed only in the surrounding mesenchyme, but not within the tooth germ. Biglycan mRNA was then expressed in the condensing mesenchyme and the dental papilla of the tooth germ. At the apposition stage (late bell stage), both decorin and biglycan mRNA were expressed in odontoblasts, resulting in a switch of the pattern of expression within the different stages of odontoblast differentiation. Decorin mRNA was expressed earlier in newly differentiating odontoblasts than biglycan. With odontoblast maturation and dentin formation, decorin mRNA expression was diminished and localized to the newly differentiating odontoblasts at the cervical region. Simultaneously, biglycan mRNA took over and extended its expression throughout the new and mature odontoblasts. Both mRNAs were expressed in the dental pulp underlying the respective odontoblasts. At P7.0, both mRNAs were weakly expressed but maintained their spatial expression patterns. Immunostaining showed that biglycan was localized in the dental papillae and pulp. In addition, all four SLRPs showed clear immunostaining in predentin, although the expressions of fibromodulin and lumican mRNAs were not identified in the tooth germs examined. The organ culture data obtained supported the histological findings that biglycan is more predominant than decorin at the apposition stage. These results were used to identify biglycan as the principal molecule among the SLRPs investigated. Our findings indicate that decorin and biglycan show spatial and temporal differential expressions and play their own tissue-specific roles in tooth development.

scholarly journals Morphometric Approach to Pulp Fibroblast Development in Tooth Germ

2014 ◽  
Vol 2014 ◽  
pp. 1-12
Author(s):  
Irina-Draga Căruntu ◽  
Sergiu Daniel Săvinescu ◽  
Cornelia Amălinei
Keyword(s):  
Form Factor ◽  
Dental Pulp ◽  
Tooth Development ◽  
Tooth Germ ◽  
Mean Value ◽  
Relative Distance ◽  
Color Segmentation ◽  
Histological Criteria ◽  
The Individual ◽  
Tooth Germs

This paper builds a morphometric framework for the analysis of dental pulp fibroblast evolution during tooth development. We investigated 15 tooth germs (cases) organized, by histological criteria, in three groups corresponding to cap, early bell, and late bell stages, respectively. Each group comprised five cases. The morphometric description used the following parameters: areaA, perimeterP—automatically extracted by a color segmentation technique, and form factor (FF)—calculated as4πA/P2. The designed framework operated at inter- and intragroup levels. The intergroup analysis quantified the differences between groups, in the sense of a relative distance (RD) adequately defined by mean-value scaling. We showed that the stage of early bell is approximately 5 times closer to late bell than to cap. The quantification procedure required concomitant information aboutA,Pparameters (asP versus Adependences, orFFvalues), whereas the procedure failed forAorPseparately used. The intragroup analysis quantified the similarity of the cases belonging to the same stage. We proved that, unlike the intergroup tests, the individual exploitation of all three descriptorsA,P, andFFis effective, yielding highly compatible results. Within any group, most cases presented RDs less than 10% from the group mean value, regardless of the descriptor type.

The role of the sonic hedgehog signalling pathway in patients with midline defects and congenital hypopituitarism

2014 ◽  
Vol 82 (5) ◽  
pp. 728-738 ◽  
Author(s):  
L.C. Gregory ◽  
C. Gaston-Massuet ◽  
C.L. Andoniadou ◽  
G. Carreno ◽  
E.A. Webb ◽  
...  
Keyword(s):  
Sonic Hedgehog ◽  
Signalling Pathway ◽  
Hedgehog Signalling ◽  
Midline Defects ◽  
Hedgehog Signalling Pathway ◽  
Congenital Hypopituitarism ◽  
Sonic Hedgehog Signalling
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