A functional analysis of dendrite enclosure by epidermal cells

Abstract

Sensory neuron morphogenesis depends on a complex interplay of intrinsic neuronal factors, systemic growth cues, interaction with growth substrates, and signaling from neighboring neuronal and non-neuronal cells. Drosophila larval dendritic arborization (da) neurons provide a valuable model for studying sensory neuron morphogenesis. The larval epidermis is innervated by four classes (C1-C4) of dendritic arborization (da) neurons that are distinguished by their unique, stereotyped morphologies and differing sensory modalities. Dendrites of different classes of da neurons innervate largely overlapping fields and are intermittently enclosed by overlying epidermal cells, with some classes of da neurons exhibiting more extensive dendrite enclosure than others. How dendrites become enclosed by epidermal cells and the functional significance of enclosure are poorly understood. To investigate roles for neuron-epidermal interactions, and enclosure in particular, I developed and described a novel dissection technique that greatly improves immunofluorescence analysis of da neurons and epidermal cells. I used this technique, in combination with genetic and quantitative approaches, to demonstrate that a cell-cell adhesion molecule, Coracle (Cora), is required in epidermal cells and da neurons to facilitate dendrite enclosure. I found that enclosure is a mechanism used by da neurons to locally restrict dendrite branching. Furthermore, I discovered novel interactions between different classes of da neurons and showed that enclosure permits coordinated innervation of their shared dendrite fields. I also demonstrated that an RNA-binding protein (RBP), Found in neurons (Fne), is required for several aspects of dendrite morphogenesis, likely by regulating dendrite-substrate interactions. I draw parallels between Fne-dependent dendrite morphogenesis and mesenchymal-to-epithelial transitions (MET) in non-neuronal tissue. My findings advance our understanding of dendrite-substrate interactions in sensory neuron morphogenesis and may have implications not only for future studies of neuronal development, but also of non-neuronal development and disease.