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Significance In comparison to the neocortex, the molecular mechanisms that contribute to neuron migration, particularly pyramidal neuron migration, and localization in the hippocampus remain for the most part unknown. The present study characterizes the role of the E3 ubiquitin ligase CRL5 during hippocampal pyramidal neuron migration. CRL5 down-regulates the small GTPase ARL4C and its associated signaling effectors, in a posttranscriptional fashion, to localize pyramidal neurons in the hippocampus. CRL5-dependent regulation of ARL4C signaling is also required for the formation of a single, apically oriented dendrite in pyramidal neurons and for its full outgrowth to the superficial strata of the hippocampus. Therefore, this study uncovers CRL5 and ARL4C signaling as crucial molecular determinants for hippocampal morphogenesis.

CRL5-dependent regulation of the small GTPases ARL4C and ARF6 controls hippocampal morphogenesis