Sonic Hedgehog Signaling is Important in Tooth Root Development

Nakatomi, Mitsushiro; Morita, I.; Eto, Kazuhiro; Ota, Masato S.

doi:10.1177/154405910608500506

Cited by 148 publications

(123 citation statements)

References 29 publications

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“…The apical edge of lingual epithelium histologically resembled an epithelial root sheath that is a unique structure found in developing molar tooth roots (Hertwig's epithelial root sheath; 3, 26). Ptc2 expression, a marker of Hertwig's epithelial root sheath in molars (14), was clearly identified in the apical edge of epithelium of the incisors of Lrp4 null mutants (Fig. 4O), suggesting that in the absence of Lrp4, epithelial cells on the lingual aspect of developing incisors were organized into root-forming structures usually seen in only molars.…”

Section: Resultsmentioning

confidence: 97%

“…To establish any causal link between loss of Shh activity and groove formation, we analyzed mice with mutations in the Shh pathway that survive after birth. The spontaneous mouse mutant, mesenchymal dysplasia, has an abnormal C terminus of the Ptc1 protein (Ptc mes/mes ) that changes Shh activity (12)(13)(14). The maxillary incisors of these mice had grooves on their labial surfaces that were also caused by a lack of enamel ( Fig.…”

Section: Resultsmentioning

confidence: 99%

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A role for suppressed incisor cuspal morphogenesis in the evolution of mammalian heterodont dentition

Ohazama

Blackburn

Porntaveetus

et al. 2009

Proc. Natl. Acad. Sci. U.S.A.

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Changes in tooth shape have played a major role in vertebrate evolution with modification of dentition allowing an organism to adapt to new feeding strategies. The current view is that molar teeth evolved from simple conical teeth, similar to canines, by progressive addition of extra "cones" to form progressively complex multicuspid crowns. Mammalian incisors, however, are neither conical nor multicuspid, and their evolution is unclear. We show that hypomorphic mutation of a cell surface receptor, Lrp4, which modulates multiple signaling pathways, produces incisors with grooved enamel surfaces that exhibit the same molecular characteristics as the tips of molar cusps. Mice with a null mutation of Lrp4 develop extra cusps on molars and have incisors that exhibit clear molar-like cusp and root morphologies. Molecular analysis identifies misregulation of Shh and Bmp signaling in the mutant incisors and suggests an uncoupling of the processes of tooth shape determination and morphogenesis. Incisors thus possess a developmentally suppressed, cuspid crown-like morphogenesis program similar to that in molars that is revealed by loss of Lrp4 activity. Several mammalian species naturally possess multicuspid incisors, suggesting that mammals have the capacity to form multicuspid teeth regardless of location in the oral jaw. Localized loss of enamel may thus have been an intermediary step in the evolution of cusps, both of which use Lrp4-mediated signaling.V ertebrates exhibit remarkable diversity in their dentitions, which is a feature of the importance of tooth shape in adaptation to new feeding strategies in evolution. Even quite closely related species of mammals can have different shapes of teeth and thus tooth development provides an excellent model for molecularly based evolutionary developmental biological studies (evo/devo). These tooth evolutional changes took place by the activation or inactivation of gene function, and thus evolutionary lost structures or gene activation/inactivation during evolution are occasionally retained as vestigial structures or latent gene activation/inactivation at embryonic stages.The current view is that all mammalian teeth evolved from simple ancestral teeth with a conical shape not dissimilar to mammalian canines (1). Mammalian heterodont dentitions contain a variety of tooth shapes and most evo/devo studies have focused solely on the molar dentition, with cuspal morphology being used as the main comparative feature between specimens (1). A cusp is a pointed or rounded projection of the tooth that is composed of both enamel and dentin, and the general consensus is that multicuspid teeth (molariform) evolved from conical teeth by progressive addition of extra "cones" (1). Incisors however are a uniquely mammalian tooth type that are neither conical nor multicuspid and their evolutional process is not understood.Among mammalian teeth, murine dentition has been used as a powerful tool for evo/devo studies because of the relative ease of gene manipulation. A major defining feature of R...

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Section: Resultsmentioning

confidence: 97%

Section: Resultsmentioning

confidence: 99%

A role for suppressed incisor cuspal morphogenesis in the evolution of mammalian heterodont dentition

Ohazama

Blackburn

Porntaveetus

et al. 2009

Proc. Natl. Acad. Sci. U.S.A.

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“…As far as the potential etiology of the root malformation is concerned, a genetic cause cannot be completely excluded, because several forms of short or absent roots in mice have recently been shown to be due to defects in various genes, for example the Nfic gene, 14 the Ptc gene, 15 and the Dkk1 gene. 16 However, none of these abnormalities affected only one type of tooth, and all lacked the typical feature of the CMD.…”

Section: Discussionmentioning

confidence: 99%

Root malformation associated with a cervical mineralized diaphragm – a distinct form of tooth abnormality?

Witt¹,

Hirt

Rutz

et al. 2014

Oral Surgery, Oral Medicine, Oral Pathology and Oral Radiology

122

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“…Tissue section in situ hybridization was conducted as previously described (34). A digoxigenin-labeled probe for Dsp mRNA (43) was prepared according to the manufacturer's protocol.…”

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confidence: 99%

Expression patterns of nestin and dentin sialoprotein during dentinogenesis in mice

et al. 2012

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Differentiated odontoblasts could not be identified by one unique phenotypic marker, but the combination of expression of dentin phosphoprotein (Dpp), dentin sialoprotein (Dsp), dentin matrix protein 1 (Dmp1), and nestin may be valuable for the assessment of these cells. However, the findings using these proteins remain controversial. This study aimed to compare two odontoblast differentiation markers: nestin and Dsp in the process of dentinogenesis in mice. We performed immunohistochemistry and/or in situ hybridization technique for nestin and Dsp using 3-week-old incisors as well as postnatal 1-day-to 8-week-old molars. Preodontoblasts began to express nestin and Dsp proteins and Dsp mRNA, which increased in their intensity according to the progress of odontoblast differentiation in both incisors and developing molars. Nestin was consistently expressed in the differentiated odontoblasts even after the completion of dentin matrix deposition. The expression of Dsp mRNA coincided with the odontoblast secretory activity for dentin matrix deposition. In contrast, other pulpal cells, predentin matrix and dentinal tubules also showed a positive reaction for Dsp protein in addition to differentiated odontoblasts. In conclusion, nestin is valuable as a differentiation marker for odontoblasts, whereas Dsp mRNA is a functional marker for their secretory activity.Dentin is a hard connective tissue that forms the bulk of the tooth, and it is a bone-like matrix characterized by multiple closely packed dentinal tubules that traverse its entire thickness and contain the cytoplasmic processes of odontoblasts, which are responsible for the formation and maintenance of the dentin. The cell bodies of the odontoblasts are aligned along the inner aspect of the dentin, beneath a layer of predentin, where they also form the peripheral boundary of the dental pulp (35). The odontoblasts are terminally differentiated ectomesenchymal cells that synthesize several collagenous and non-collagenous proteins (NCPs) (45). The morphologically discernible differentiation of the odontoblast begins with the dental papilla cells adjacent to the inner enamel epithelium (7). The dental papilla cells adjoining the acellular zone rapidly enlarge and elongate to become preodontoblasts first and then odontoblasts as their cytoplasm increases in volume to contain increasing amounts of proteinsynthesizing organelles. The morphology of odontoblasts reflects their functional activity and ranges from an active synthetic phase to a quiescent phase (35). However, the preferred use of terminology regarding the classification of odontoblasts is controversial, because several terms for differentiated odontoblasts have been used by different researchers, i.e., secretory, transitional, and aged odontoblasts (12), young and old odontoblasts (51), or

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Sonic Hedgehog Signaling is Important in Tooth Root Development

Cited by 148 publications

References 29 publications

A role for suppressed incisor cuspal morphogenesis in the evolution of mammalian heterodont dentition

A role for suppressed incisor cuspal morphogenesis in the evolution of mammalian heterodont dentition

Root malformation associated with a cervical mineralized diaphragm – a distinct form of tooth abnormality?

Expression patterns of nestin and dentin sialoprotein during dentinogenesis in mice

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