The RNA-binding protein Nab2 regulates the proteome of the developing Drosophila brain.

The human ZC3H14 gene, which encodes a ubiquitously expressed polyadenosine zinc finger RNA-binding protein, is mutated in an inherited form of autosomal recessive, nonsyndromic intellectual disability. To gain insight into neurological functions of ZC3H14, we previously developed a Drosophila melanogaster model of ZC3H14 loss by deleting the fly ortholog, Nab2. Studies in this invertebrate model revealed that Nab2 controls final patterns of neuron projection within fully developed adult brains, but the role of Nab2 during development of the Drosophila brain is not known. Here, we identify roles for Nab2 in controlling the dynamic growth of axons in the developing brain mushroom bodies, which support olfactory learning and memory, and regulating abundance of a small fraction of the total brain proteome. The group of Nab2-regulated brain proteins, identified by quantitative proteomic analysis, includes the microtubule-binding protein Futsch, the neuronal Ig-family transmembrane protein turtle, the glial:neuron adhesion protein contactin, the Rac GTPase-activating protein tumbleweed, and the planar cell polarity factor Van Gogh, which collectively link Nab2 to the processes of brain morphogenesis, neuroblast proliferation, circadian sleep/wake cycles, and synaptic development. Overall, these data indicate that Nab2 controls the abundance of a subset of brain proteins during the active process of wiring the pupal brain mushroom body and thus provide a window into potentially conserved functions of the Nab2/ZC3H14 RNA-binding proteins in neurodevelopment.

The Nab2 RNA-binding protein patterns dendritic and axonal projections through a planar cell polarity-sensitive mechanism.

RNA-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 RNA-binding protein 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 RNA-binding protein Ataxin-2. However, neuronal signaling pathways regulated by Nab2 and their potential roles outside of mushroom body axons remain undefined. Here, we present an analysis of a brain proteomic dataset that indicates that multiple planar cell polarity proteins are affected by Nab2 loss, and couple this with genetic data that demonstrate that Nab2 has a previously unappreciated role in restricting the growth and branching of dendrites that elaborate from larval body-wall sensory neurons. Further analysis confirms that Nab2 loss sensitizes sensory dendrites to the genetic dose of planar cell polarity components and that Nab2-planar cell polarity genetic interactions are also observed during Nab2-dependent control of axon projection in the central nervous system mushroom bodies. Collectively, these data identify the conserved Nab2 RNA-binding protein as a likely component of post-transcriptional mechanisms that limit dendrite growth and branching in Drosophila sensory neurons and genetically link this role to the planar cell polarity pathway. Given that mammalian ZC3H14 localizes to dendritic spines and controls spine density in hippocampal neurons, these Nab2-planar cell polarity genetic data may highlight a conserved path through which Nab2/ZC3H14 loss affects morphogenesis of both axons and dendrites in diverse species.

Stimulus Parameters Underlying Sound-Symbolic Mapping of Auditory Pseudowords to Visual Shapes.

Sound symbolism refers to non-arbitrary mappings between the sounds of words and their meanings and is often studied by pairing auditory pseudowords such as "maluma" and "takete" with rounded and pointed visual shapes, respectively. However, it is unclear what auditory properties of pseudowords contribute to their perception as rounded or pointed. Here, we compared perceptual ratings of the roundedness/pointedness of large sets of pseudowords and shapes to their acoustic and visual properties using a novel application of representational similarity analysis (RSA). Representational dissimilarity matrices (RDMs) of the auditory and visual ratings of roundedness/pointedness were significantly correlated crossmodally. The auditory perceptual RDM correlated significantly with RDMs of spectral tilt, the temporal fast Fourier transform (FFT), and the speech envelope. Conventional correlational analyses showed that ratings of pseudowords transitioned from rounded to pointed as vocal roughness (as measured by the harmonics-to-noise ratio, pulse number, fraction of unvoiced frames, mean autocorrelation, shimmer, and jitter) increased. The visual perceptual RDM correlated significantly with RDMs of global indices of visual shape (the simple matching coefficient, image silhouette, image outlines, and Jaccard distance). Crossmodally, the RDMs of the auditory spectral parameters correlated weakly but significantly with those of the global indices of visual shape. Our work establishes the utility of RSA for analysis of large stimulus sets and offers novel insights into the stimulus parameters underlying sound symbolism, showing that sound-to-shape mapping is driven by acoustic properties of pseudowords and suggesting audiovisual cross-modal correspondence as a basis for language users' sensitivity to this type of sound symbolism.