β-catenin is Required in Odontoblasts for Tooth Root Formation

Abstract

The tooth root is an important part of the tooth that works together with the surrounding periodontium to maintain the tooth in the alveolar socket. The root develops after crown morphogenesis. While the molecular and cellular mechanisms of early tooth development and crown morphogenesis have been extensively studied, little is known about the molecular mechanisms controlling tooth root formation. Here, we show that β-catenin is strongly expressed in odontoblast-lineage cells and is required for root formation. Tissue-specific inactivation of β-catenin in developing odontoblasts produced molars lacking roots and aberrantly thin incisors. At the beginning of root formation in the mutant molars, the cervical loop epithelium extended apically to form Hertwig's epithelial root sheath (HERS), but root odontoblast differentiation was disrupted and followed by the loss of some HERS inner layer cells. However, the outer layer of the HERS extended without the root, and the mutant molars finally erupted. The periodontal tissues extensively invaded the dental pulp. These results indicate that there is a cell-autonomous requirement for Wnt/β-catenin signaling in the dental mesenchyme for root formation.

An Nfic-hedgehog signaling cascade regulates tooth root development

“…Some models, such as Osr2-Cre;Smad4 fl/fl and K14-Cre;Smad4 fl/fl (Huang et al, 2010), show phenotypes in early stages of tooth development, but it is hard to determine whether the root defect is secondary to the crown defect. Other models, including OC-Cre (Bae et al, 2013b;Gao et al, 2009;Kim et al, 2013;Zhang et al, 2013), Col1a1-Cre (Kim et al, 2012) and Sp7-Cre (Rakian et al, 2013;Wang et al, 2013), take effect too late, only targeting differentiated cells. Here, we used the Gli1-CreERT/loxP system to target the early progenitor cells for root development.…”

“…Although several reports have described root defect phenotypes following targeted gene mutation, there has not been a systematic analysis of postnatal root development (Bae et al, 2013b;Kim et al, 2013;Wang et al, 2013). Towards this end, we analyzed serial sagittal sections of the first mandibular molar in mice from PN0 to PN21 using HE staining.…”

Three-Dimensional Printed Multiphase Scaffolds for Regeneration of Periodontium Complex

“…[4][5][6][7] The field of tooth regeneration has grown robustly. [8][9][10][11][12][13][14][15][16][17][18][19][20] The ambitious goal to regenerate an entire tooth, including the enamel, has encountered several barriers, such as the unavailability of patient compatible, postnatal stem/progenitor cells, and lack of strategy to derive functional ameloblasts. 12 A less ambitious and pragmatic goal to regenerate mineralized tooth roots has gained substantial momentum.…”

The Role of Autonomous Wntless in Odontoblastic Differentiation of Mouse Dental Pulp Cells

“…Zhu et al 14) reported that tooth morphogenesis is arrested in tissuespecific ablation of Wls in the dental epithelium. We recently found that tissue-specific inactivation or constitutive stabilization of β-catenin (β-Cat) leads to disrupted odontoblast differentiation in roots or excessive dentin formation, respectively 15,16) . In addition, deletion of the Wls gene in odontoblasts appears to reduce canonical Wnt activity, leading to inhibition of odontoblast maturation and root elongation 17) .…”