Wnt10
Wnt10 refers mainly to the related ligands WNT10A and WNT10B, which regulate organ development, cell proliferation, differentiation, and tissue patterning through Wnt/β-catenin signaling[1]. Mechanistically, WNT10A supports ectoderm-derived tissues by maintaining β-catenin activity, epithelial progenitor proliferation, and KLF4-mediated differentiation[2]. In disease genetics, WNT10A variants associate with ectodermal dysplasia, selective tooth agenesis, abnormal tooth shape, and stronger dental severity in bi-allelic cases[3][4]. Compared with WNT10A, WNT10B shows clearer experimental relevance to skeletal and adipose biology, because Wnt10b transgenic mice show increased bone mass and resistance to age- or estrogen-deficiency bone loss[5]. Wnt10b also shifts mesenchymal cell fate toward osteoblastogenesis by inducing Runx2, Dlx5, and osterix while suppressing adipogenic regulators[5]. In tooth models, combined Wnt10a/Wnt10b mutation causes reduced tooth number and severe root or enamel hypoplasia, supporting functional redundancy between the isoforms[1]. Therefore, Wnt10 research should distinguish WNT10A-focused ectodermal and dental models from WNT10B-focused bone, adipogenesis, and β-catenin pathway models[1][5].
References:
- [1]. Yoshinaga K, et al. Effects of Wnt10a and Wnt10b Double Mutations on Tooth Development. Genes (Basel). 2023 Jan 28;14(2):340. [Content Brief]
- [2]. Xu M, et al. WNT10A mutation causes ectodermal dysplasia by impairing progenitor cell proliferation and KLF4-mediated differentiation. Nat Commun. 2017 Jun 7;8:15397. [Content Brief]
- [3]. Mues G, et al. The WNT10A gene in ectodermal dysplasias and selective tooth agenesis. Am J Med Genet A. 2014 Oct;164A(10):2455-60. [Content Brief]
- [4]. Yang J, et al. Taurodontism, variations in tooth number, and misshapened crowns in Wnt10a null mice and human kindreds. Mol Genet Genomic Med. 2015 Jan;3(1):40-58. [Content Brief]
- [5]. Bennett CN, et al. Regulation of osteoblastogenesis and bone mass by Wnt10b. Proc Natl Acad Sci U S A. 2005 Mar 1;102(9):3324-9. [Content Brief]
