F3, also known as Contactin, is a neuronal cell adhesion molecule belonging to the immunoglobulin superfamily. It has a modular structure with multiple binding sites, displaying heterophilic binding activities. F3 is involved in axogenesis, myelination, neuron-glial contacts, and organization of axonal subdomains at the node of Ranvier. It interacts with L1 family of Ig-CAMs, extracellular matrix components, and RPTPbeta/phosphacan, influencing axonal growth, fasciculation, and sensory axon guidance [1].

F3-deficient mice display severe ataxia due to defects in axonal and dendritic projections in the cerebellum, as well as nerve influx conduction defects from disrupted axo-glial contacts at paranodes [1]. In the hippocampus of mice, both chronic restraint stress and chronic social defeat stress decrease the expression of F3/Contactin. Over-expression of hippocampal F3/Contactin can prevent chronic stress-induced depressive-like behaviors, reverse the dysfunction in BDNF-CREB signaling and neurogenesis, while knockdown of it abolishes the protecting effects of vortioxetine against chronic stress [2].

In conclusion, F3 is crucial for neural development, playing a role in axonal and dendritic projections, myelination, and axo-glial contacts. In addition, it is implicated in depression, as its expression in the hippocampus is associated with stress-induced depressive-like behaviors and the action of antidepressants. The study of F3 using mouse models helps to understand its biological functions and its potential as a therapeutic target for depression.