EphA7, a member of the Eph receptor family, is widely involved in cell-cell signal transduction, regulating cell proliferation, differentiation, and playing a role in the development of neural tubes and the brain [1]. It may participate in various signaling pathways related to cell growth, migration, and apoptosis. Genetic models, such as gene knockout mouse models, can be valuable tools for studying its functions.

In EphA7 -/- mice, hindlimb muscles have fewer myofibers at birth, which are reduced in size with fewer myonuclei and fewer precursor cells throughout postnatal life. Adult EphA7 -/- mice have reduced satellite cell numbers and show delayed and protracted muscle regeneration, indicating that EphA7 promotes myogenic differentiation via cell-cell contact [4]. Also, in some neurodevelopmental disorders, deletions in the EPHA7 gene are associated with the condition. In 12 patients from nine unrelated pedigrees, similar deletions were reported, with four having tiny deletions involving only EPHA7, suggesting its critical role in a neurodevelopmental disability phenotype [3]. In esophageal squamous cell carcinoma, EphA7 is upregulated by activated STAT3, and its silence suppresses tumor growth, indicating its role in promoting cancer progression [2].

In conclusion, EphA7 is crucial for normal development, including myogenic and neural development. In disease conditions, especially cancer, EphA7 shows potential as a diagnostic marker and treatment target. The use of KO mouse models has been instrumental in revealing its functions in normal biological processes and disease-related mechanisms.

References:

1. Chen, Xiangyi, Yu, Dechen, Zhou, Haiyu, Guo, Taowen, Zhang, Kun. 2022. The role of EphA7 in different tumors. In Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico, 24, 1274-1289. doi:10.1007/s12094-022-02783-1. https://pubmed.ncbi.nlm.nih.gov/35112312/

2. Wang, Li, Zhao, Qiao-Feng, Yang, Bing-Bing, Tian, Fang, Wu, Qing-Hua. 2023. STAT3-EphA7 axis contributes to the progression of esophageal squamous cell carcinoma. In Acta oncologica (Stockholm, Sweden), 62, 1757-1766. doi:10.1080/0284186X.2023.2259601. https://pubmed.ncbi.nlm.nih.gov/37738252/

3. Lévy, Jonathan, Schell, Bérénice, Nasser, Hala, Verloes, Alain, Tabet, Anne-Claude. 2021. EPHA7 haploinsufficiency is associated with a neurodevelopmental disorder. In Clinical genetics, 100, 396-404. doi:10.1111/cge.14017. https://pubmed.ncbi.nlm.nih.gov/34176129/

4. Arnold, Laura L, Cecchini, Alessandra, Stark, Danny A, Zino, Sammy, Cornelison, Ddw. 2020. EphA7 promotes myogenic differentiation via cell-cell contact. In eLife, 9, . doi:10.7554/eLife.53689. https://pubmed.ncbi.nlm.nih.gov/32314958/