Sonic Hedgehog Signaling and Tooth Development

Abstract

Sonic hedgehog (Shh) is a secreted protein with important roles in mammalian embryogenesis. During tooth development, Shh is primarily expressed in the dental epithelium, from initiation to the root formation stages. A number of studies have analyzed the function of Shh signaling at different stages of tooth development and have revealed that Shh signaling regulates the formation of various tooth components, including enamel, dentin, cementum, and other soft tissues. In addition, dental mesenchymal cells positive for Gli1, a downstream transcription factor of Shh signaling, have been found to have stem cell properties, including multipotency and the ability to self-renew. Indeed, Gli1-positive cells in mature teeth appear to contribute to the regeneration of dental pulp and periodontal tissues. In this review, we provide an overview of recent advances related to the role of Shh signaling in tooth development, as well as the contribution of this pathway to tooth homeostasis and regeneration.

The intraspecific diversity of tooth morphology in the large‐spotted catshark Scyliorhinus stellaris: insights into the ontogenetic cues driving sexual dimorphism

“…To our knowledge, there are very scarce genetic data available on tooth morphogenesis in S. stellaris (Rasch et al, 2016) but gene regulatory networks involved in elasmobranch tooth development have been investigated in S. canicula. The expression of classical developmental genes was characterized in tooth buds (Debiais-Thibaud et al, 2011, 2015Martin et al, 2016;Rasch et al, 2016), including the well-known signaling factor Shh that acts as both a tooth bud initiation signal and a proliferation signal during tooth morphogenesis (Berio and Debiais-Thibaud, 2019;Hosoya et al, 2020). Data on the physical features that could constrain tooth bud growth within the dental lamina are even scarcer although previous studies on mammals emphasized that a modification of the tooth bud physical environment can modify the final shape of a tooth (Renvoisé et al, 2017).…”

Hedgehog signaling activates a heterochronic gene regulatory network to control differentiation timing across lineages

“…These observations suggest that precocious progenitor differentiation, potentially as a result of abrogated Hh signaling, may be a significant mechanism underlying CHD. Hosoya et al, 2020;Ingham and Placzek, 2006;Ingham et al, 2011;Jiang and Hui, 2008;Lee et al, 2016;McMahon et al, 2003;Singh et al, 2015;Wallace, 2008). Global disruption of Hh signaling during embryogenesis causes pleiotropic developmental syndromes, including VACTERL syndrome, Gorlin Syndrome, holoprosencephaly and Greig cephalopolysyndactyly syndrome (Hui and Angers, 2011;McMahon et al, 2003;Ngan et al, 2012;Nieuwenhuis and Hui, 2005).…”

Integrated Analyses of Mouse Stem Cell Transcriptomes Provide Clues for Stem Cell Maintenance and Transdifferentiation

“…Although the capacity of tissue regeneration in mammals is progressively lost during development, several tissues and organs still maintain stem cell niches that produce progeny cells which promote tissue regeneration (Adams and Scadden, 2006;Oatley et al, 2009). Accumulating evidence also indicates that the isolation of stem cells from others tissue or organs, including the intestine, liver, and teeth, is feasible and that those stem cells can maintain the regeneration of their respective tissues under certain circumstances (Hosoya et al, 2020;Takahashi and Shiraishi, 2020). The best-characterized types of adult stem cells in mammals are hematopoietic (HSCs), neural (NSCs), mesenchymal (MSCs), and spermatogonia (SSCs) stem cells.…”