The Drosophila RNA binding protein Nab2 patterns dendritic arbors and axons via the planar cell polarity pathway

Abstract

AbstractRNA binding proteins support neurodevelopment by modulating numerous steps in post-transcriptional regulation, including splicing, export, translation, and turnover of mRNAs that can traffic into axons and dendrites. One such RBP is ZC3H14, which is lost in an inherited intellectual disability. The Drosophila melanogaster ZC3H14 ortholog, Nab2, localizes to neuronal nuclei and cytoplasmic ribonucleoprotein granules, and is required for olfactory memory and proper axon projection into brain mushroom bodies. Nab2 can act as a translational repressor in conjunction with the Fragile-X mental retardation protein homolog Fmr1 and shares target RNAs with the Fmr1-interacting RBP Ataxin-2. However, neuronal signaling pathways regulated by Nab2 and their potential roles outside of mushroom body axons remain undefined. Here, we demonstrate that Nab2 restricts branching and projection of larval sensory dendrites via the planar cell polarity pathway, and that this link may provide a conserved mechanism through which Nab2/ZC3H14 modulates projection of both axons and dendrites. Planar cell polarity proteins are enriched in a Nab2-regulated brain proteomic dataset. Complementary genetic data indicate that Nab2 guides dendrite and axon growth through the planar-cell-polarity pathway. Analysis of the core planar cell polarity protein Vang, which is depleted in the Nab2 mutant whole-brain proteome, uncovers selective and dramatic loss of Vang within axon/dendrite-enriched brain neuropil relative to brain regions containing cell bodies. Collectively, these data demonstrate that Nab2 regulates dendritic arbors and axon projection by a planar-cell-polarity-linked mechanism and identify Nab2 as required for accumulation of the core planar cell polarity factor Vang in distal neuronal projections.