Viriot, L. | bioRxiv Science

bioRxiv2022

Notch signaling pathway in tooth shape variations

Evolutionary changes in vertebrates are linked to genetic alterations that often affect tooth-crown shape, which is a criterion of speciation events. The Notch pathway is highly conserved between species and controls morphogenetic processes in most developing organs, including teeth. Epithelial loss of the Notch-ligand Jagged1 in developing mouse molars affects the location, size and interconnections of their cusps that lead to minor tooth-crown shape modifications convergent to those observed along Muridae evolution. These alterations are due to the modulation of numerous genes, where Notch signaling is a hub for essential morphogenetic networks. A three-dimensional metamorphosis approach allowed tooth morphology prediction in individuals carrying Jagged1 mutations. These results shed new light on Notch/Jagged1-mediated signaling as one of the crucial components for dental variations in evolution. Significance statementDental microevolution changes in vertebrates are regulated by the Notch signaling pathway.

developmental biology↗

bioRxiv2020

Hedgehog signalling regulates patterning of the murine and human dentitions through Gas1 co-receptor function

The mammalian dentition exhibits wide numerical and morphological variation between different species. The regulation of dental pattern is achieved through complex reiterative molecular signalling interactions that occur through multiple stages of tooth development. We show that mice with loss-of-function in the Hedgehog co-receptor Gas1 have variation in size, morphology and number of teeth within the molar dentition. Specifically, premolar-like supernumerary teeth are present with high penetrance, arising through survival and continued development of vestigial tooth germs. We further demonstrate that Gas1 function in cranial neural crest cells is essential for the regulation of tooth number, acting to restrict Wnt signalling in vestigial tooth germs through facilitation of Shh signalling. Moreover, regulation of tooth number is independent of the additional Hedgehog co-receptors Cdon and Boc. Interestingly, further reduction of Shh pathway activity in a Gas1 mutant background leads to fusion of the molar field and ultimately, developmental arrest of tooth development rather than exacerbating the supernumerary phenotype. Finally, we demonstrate defective coronal morphology in the molar dentition of human subjects carrying GAS1 missense mutations, suggesting that regulation of Hedgehog signalling through GAS1 is also essential for normal patterning of the human dentition.

developmental biology↗