The ELAV/Hu protein Found in neurons regulates cytoskeletal and ECM adhesion inputs for space-filling dendrite growth

Dendritic arbor morphology influences how neurons receive and integrate extracellular signals. We show that the ELAV/Hu family RNA-binding protein Found in neurons (Fne) is required for space-filling dendrite growth to generate highly branched arbors of Drosophila larval class IV dendritic arborization neurons. Dendrites of fne mutant neurons are shorter and more dynamic than in wild-type, leading to decreased arbor coverage. These defects result from both a decrease in stable microtubules and loss of dendrite-substrate interactions within the arbor. Identification of transcripts encoding cytoskeletal regulators and cell-cell and cell-ECM interacting proteins as Fne targets using TRIBE further supports these results. Analysis of one target, encoding the cell adhesion protein Basigin, indicates that the cytoskeletal defects contributing to branch instability in fne mutant neurons are due in part to decreased Basigin expression. The ability of Fne to coordinately regulate the cytoskeleton and dendrite-substrate interactions in neurons may shed light on the behavior of cancer cells ectopically expressing ELAV/Hu proteins. Author summary Different types of neurons have different sizes and shapes that are tailored to their particular functions. In the fruit fly larva, a set of sensory neurons called class IV da neurons have highly branched trees of dendrites that cover the epidermis to sense potentially harmful stimuli. Neurons whose dendrites completely fill the territory they sample are also found in zebrafish, worms, mice and humans. We show that an RNA-binding protein called Fne plays an important role in coordinating different contributions to dendrite branching in class IV da neurons by impacting the organization of the cytoskeleton within the neuron and the ability of the dendrite to contact the substratum outside of it. The identification of mRNAs that code for cytoskeleton regulators and adhesive proteins as targets of Fne using a genome-wide approach further supports these results. While the ability of Fne to exert control over such proteins is crucial to generating the space-filling growth of neurons, it can be deleterious if not properly employed, such as when the homologs of Fne are expressed in cancer cells.