Sema6b, a member of the semaphorin axon-guidance family, plays diverse roles in biological processes. It is involved in axon guidance, neuronal development including spine formation and maturation, and may be associated with immune-related pathways. Genetic models such as gene knockout mice are valuable for studying its functions [2].

In hepatitis B virus-related acute-on-chronic liver failure (HBV-ACLF), Sema6b knockout mice showed improved liver functions, reduced inflammatory responses, and decreased hepatocyte apoptosis. Transcriptome analysis of their liver tissue revealed significant down-regulation of inflammation-related pathways. This indicates that Sema6b exacerbates liver failure through macrophage-mediated systemic inflammation and hepatocyte apoptosis, and could be a potential diagnostic biomarker and early treatment target for HBV-ACLF [1]. In neuronal development, knockdown of Sema6b in neuronal cultures impaired spine density and maturation, and in chicken embryos, mutated forms of Sema6b failed to rescue the normal axon pathway after endogenous Sema6b knockdown, highlighting its role in neuronal development [2].

In conclusion, Sema6b is crucial in neuronal development and has a significant impact on liver failure progression. Gene knockout models, especially in the context of HBV-ACLF, have revealed its role in inflammation and apoptosis, providing potential therapeutic targets for this life-threatening liver condition. Additionally, its role in neuronal development underscores its importance in neurobiology [1,2].

References:

1. Yang, Hui, Cai, Qun, Xin, Jiaojiao, Shi, Dongyan, Li, Jun. 2024. SEMA6B induces macrophage-mediated inflammation and hepatocyte apoptosis in hepatitis B virus-related acute-on-chronic liver failure. In Theranostics, 14, 5200-5218. doi:10.7150/thno.97007. https://pubmed.ncbi.nlm.nih.gov/39267780/

2. Cordovado, Amélie, Schaettin, Martina, Jeanne, Médéric, Toutain, Annick, Vuillaume, Marie-Laure. . SEMA6B variants cause intellectual disability and alter dendritic spine density and axon guidance. In Human molecular genetics, 31, 3325-3340. doi:10.1093/hmg/ddac114. https://pubmed.ncbi.nlm.nih.gov/35604360/