Wnt10a, a secreted glycoprotein, is crucial for ectodermal organogenesis and tissue regeneration, participating in signaling pathways essential to these processes [1]. It was first linked to human disorders in 2006, specifically cleft lip with/without cleft palate [1].

In mice, whole-tissue and dental epithelium-specific knockout (KO) of Wnt10a (EIIa-Cre;Wnt10aflox/flox and K14-Cre;Wnt10aflox/flox) led to absence or apical location of root furcation in molars, resembling taurodontism seen in patients with biallelic Wnt10a mutation [2]. Epithelial knockout of Wnt10a decreased epithelial cell proliferation at the cervical region of the molar just before root morphogenesis, while increasing pulpal mesenchymal cell proliferation in the presumptive root furcating region later [2]. Also, a Wnt10a-Notch signaling axis was found to be crucial for modulating Hertwig's epithelial root sheath (HERS) cell proper proliferation and horizontal-oriented division during tooth root furcation morphogenesis in K14-Cre;Wnt10afl/fl mice [4]. Moreover, deletion of Wnt10a in mice caused spatial memory impairment, anxiety-like behavior, decreased neurogenesis, impaired synaptic function, and induced hippocampal neuroinflammation, potentially through the β-catenin signaling pathway [3].

In conclusion, Wnt10a is essential for ectodermal organ development, especially tooth root morphogenesis, and also plays a role in hippocampal function. Studies using KO and conditional knockout (CKO) mouse models have significantly contributed to understanding its functions in these processes and their related disease conditions, such as taurodontism and hippocampal neurodegeneration [2,3,4].