Atypical cadherin, Fat2, regulates axon terminal organization in the developing olfactory receptor neurons.

The process of how neuronal identity confers circuit organization is intricately related to the mechanisms underlying neurodegeneration and neuropathologies. Modeling this process, the olfactory circuit builds a functionally organized topographic map, which requires widely dispersed neurons with the same identity to converge their axons into one a class-specific neuropil, a glomerulus. In this article, we identified Fat2 (also known as Kugelei) as a regulator of class-specific axon organization. In mutants, axons belonging to the highest -expressing classes present with a more severe phenotype compared to axons belonging to low -expressing classes. In extreme cases, mutations lead to neural degeneration. Lastly, we found that Fat2 intracellular domain interactors, APC1/2 (Adenomatous polyposis coli) and (Drop out), likely orchestrate the cytoskeletal remodeling required for axon condensation. Altogether, we provide a potential mechanism for how cell surface proteins' regulation of cytoskeletal remodeling necessitates identity specific circuit organization.