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Background  Circuit formation in the nervous system essentially relies on the proper development of neurons and their processes. In this context, the ubiquitin ligase Nedd4 is a crucial modulator of axonal and dendritic branching.    Results  Herein we characterize the Nedd4-binding protein 3 (N4BP3), a Fezzin family member, during nerve cell development. In developing rat primary hippocampal neurons, endogenous N4BP3 localizes to neuronal processes, including axons and dendrites. Transient  in vitro  knockdown of N4BP3 in hippocampal cultures during neuritogenesis results in impaired branching of axons and dendrites. In line with these findings,  in vivo  knockdown of n4bp3 in  Xenopus laevis  embryos results in severe alteration of cranial nerve branching.    Conclusions  We introduce N4BP3 as a novel molecular element for the correct branching of neurites in developing neurons and propose a central role for an N4BP3-Nedd4 complex in neurite branching and circuit formation.

The Nedd4-binding protein 3 (N4BP3) is crucial for axonal and dendritic branching in developing neurons