Dchs1, short for Dachsous Cadherin-Related 1, is a calcium-dependent adhesion membrane protein. It functions as a key component in multiple developmental processes, being involved in pathways like planar cell polarity (PCP) and potentially the Hippo pathway [3,4]. It is of great biological importance in mammalian tissue development. Genetic models, especially KO/CKO mouse models, are valuable for studying its functions.

In mouse models, Dchs1-Fat4 mutants mimic the craniofacial phenotype of human Van Maldergem syndrome due to mutations in DCHS1 and FAT4. Dchs1-Fat4 signalling is essential for osteoblast differentiation; its loss leads to increased osteoprogenitor proliferation and delayed osteoblast differentiation, associated with increased Yap-Tead activity [1]. In vertebrae development, Dchs1-Fat4 signalling controls cell proliferation, and the key defect in Dchs1 mutant mice is decreased proliferation in the early sclerotome [3]. In skeletal morphogenesis, the Dchs1-Fat4 planar cell polarity pathway controls cell orientation in early skeletal condensation to define the shape of the mouse sternum [4]. In kidney development, Dchs1 mutation in mice causes abnormal arrangement of cap mesenchyme cells, impairment of nephron morphogenesis, and reduced ureteric bud branching [5]. Mutations in Dchs1 also cause mitral valve prolapse in mice and humans, with Dchs1 deficiency leading to altered migration and cellular patterning in mitral valve interstitial cells [6].

In conclusion, Dchs1 is crucial for multiple biological processes including osteoblast differentiation, vertebrae development, skeletal morphogenesis, kidney development, and mitral valve morphogenesis. The use of Dchs1 KO/CKO mouse models has significantly contributed to understanding its role in these processes and associated diseases such as Van Maldergem syndrome, mitral valve prolapse, and potentially pediatric urinary tract infections as indicated by the association of DCHS1 DNA copy number loss with UTI risk in children [1,2,3,4,5,6].