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. 2023 Jan 30;12(2):220. doi: 10.3390/biology12020220

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© 2023 by the authors.

Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).

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Hypothetical flowchart of pathogenetic pathways for mesiodens formation as a result of LRP4 variants. When the mutant Lrp4 does not properly interact with Sostdc1 as a result of mutation, it upregulates Wnt/β-catenin signaling by forming the Wnt-Fzd-Lrp4 complex. The resulting increase in WNT/β-catenin signaling and/or broadening of the placodal regions is responsible for the subsequent formation of the supernumerary teeth. Overactivation of WNT/β-catenin signaling leading to ectopic expression of SHH signaling is the key to mesiodens formation [3,4,6,12].