Sema6a, a multifunctional transmembrane semaphorin protein, is involved in various cellular processes. It plays roles in axon guidance, cell migration, and is associated with pathways like Wnt/β -catenin, and its receptor Plexin-A2 is crucial in mediating its effects [1,2]. It is also important in processes such as vascular development, adult angiogenesis, and bone remodeling, and is implicated in several diseases including cancer, delayed puberty, and osteolytic diseases [1-3]. Genetic models are valuable for studying Sema6a's functions.

In zebrafish, loss of Sema6A or its receptor PlexinA2 leads to smaller eyes and improper retinal patterning. Rescue experiments showed that while the intracellular domain of Sema6A is not required for eye size and retinal patterning, it is essential for retinal integrity, Müller glia characteristics, and protecting against retinal cell death [3]. In Plexin-A4 knockout mice, Sema6A expressed in oligodendrocyte precursor cells (OPCs) was found to be involved in their autonomous migration through ligand-receptor interaction with Plexin-A4 expressed in surrounding cells. Sema6A knockdown in an in vitro migration assay repressed the migration of an OPCs model (FBD-102b cells) [4].

In conclusion, Sema6a is essential for various biological processes. Its role in the retina and OPC migration has been revealed through animal models. In the context of diseases, it has been associated with conditions like delayed puberty, clear cell renal cell carcinoma, and osteolytic diseases, highlighting its potential as a therapeutic target in these disease areas [1-3].