Department of Orthodontics and Dentofacial Orthopedics, Tokushima University Graduate School of Biomedical Sciences, 3-18-15 Kuramoto-cho, Tokushima 770-8504, Japan.
Nakano-Cho niconicoKamKam Dental and Orthodontics, 1-31 Nakano-cho, Tokushima 770-0932, Japan.
Genes (Basel). 2023 Jan 28;14(2):340. doi: 10.3390/genes14020340.
WNT molecules are the regulators of various biological functions, including body axis formation, organ development, and cell proliferation and differentiation. WNTs have been extensively studied as causative genes for an array of diseases. and , which are considered to be genes of the same origin, have been identified as causative genes for tooth deficiency in humans. However, the disrupted mutant of each gene does not show a decrease in teeth number. A negative feedback loop, interacting with several ligands based on a reaction-diffusion mechanism, was proposed to be important for the spatial patterning of tooth formation, and WNT ligands have been considered to play a pivotal role in controlling tooth patterning from mutant phenotypes of LDL receptor-related proteins (LRPs) and WNT co-receptors. The and double-mutants demonstrated severe root or enamel hypoplasia. In and mice, changes in the feedback loop may collapse the modulation of fusion or split a sequence of tooth formation. However, in the double-knockout mutant, a decrease in the number of teeth was observed, including the upper incisor or third molar in both jaws. These findings suggest that there may be a functional redundancy between and and that the interaction between the two genes functions in conjunction with other ligands to control the spatial patterning and development of teeth.
WNT 分子是各种生物功能的调节剂，包括身体轴形成、器官发育以及细胞增殖和分化。WNT 作为一系列疾病的致病基因已被广泛研究。 和 ，被认为是同源基因，已被确定为人类牙齿缺失的致病基因。然而，每个基因的突变体并没有表现出牙齿数量的减少。基于反应扩散机制的相互作用，一个负反馈回路被认为对于牙齿形成的空间模式很重要，WNT 配体被认为在控制牙齿模式形成中发挥了关键作用，从 LDL 受体相关蛋白 (LRP) 和 WNT 共受体的突变表型中可以看出。 和 双突变体表现出严重的根或牙釉质发育不全。在 和 小鼠中，反馈回路的变化可能会破坏融合或分裂牙齿形成序列的调节。然而，在双敲除突变体中，观察到牙齿数量减少，包括上下颌的中切牙或第三磨牙。这些发现表明 和 之间可能存在功能冗余，并且两个基因之间的相互作用与其他配体一起发挥作用，以控制牙齿的空间模式和发育。
