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Title: Dendritically Localized mRNAs Regulate Class IV Dendritic Arborization Neuron Morphology in Drosophila melanogaster
Authors: Edmund, Hendia
Advisors: Gavis, Elizabeth R
Contributors: Molecular Biology Department
Keywords: cora
Dendritic localization
Subjects: Molecular biology
Issue Date: 2019
Publisher: Princeton, NJ : Princeton University
Abstract: The organization of neuronal dendrites is strictly controlled and maintained during development. These specialized structures adopt a specific morphology that aids in the processing and integration of external inputs. We have shown that post-transcriptional gene regulation, more specifically dendritic RNA localization and local translation, plays an important role in the morphogenesis of a subset of Drosophila peripheral sensory neurons, the class IV dendritic arborization (da) neurons. In a genome-wide screen to identify dendritically localized mRNAs, 47 genes were identified and RNAi knockdown of 18 genes led to defects in dendrite morphogenesis. To further investigate mRNA localization in class IV da neurons, we focused on coracle (cora). Cora is expressed in both the epidermis and the neuron to mediate dendrite enclosure by the epidermis. Enclosure limits dendrite branching and allows for the coexistence of different classes of da neurons within the same receptive field. cora RNA localizes to the dendrites of class IV da neurons. The cora 3'UTR is both necessary and sufficient to confer dendritic localization, and contains three structures predicted to be recognized by the RNA binding protein Staufen (Stau). Stau is required for dendritic localization of cora mRNA. stau mutant class IV da neurons are overbranched, like cora mutants, and also exhibit increased intra-dendrite crossings, a result of a loss of self-avoidance. Dendrite overbranching in stau mutant neurons is rescued by cora overexpression. Additionally, stau/cora transheterozygotes exhibit significantly worse branching defects than stau/+ neurons. Together these results suggest that Stau-mediated cora regulation controls branching in class IV da neurons. We also performed functional analysis of another candidate from the screen, frayed (fray), which encodes a serine/threonine (Ser/Thr) kinase involved in axon ensheathment and fasciculation. Knockdown of fray in class IV da neurons results in a significant increase in the number of terminal branches. Fray is part of the Wnk/Wnt pathway and is phosphorylated by a kinase called Wnk, to regulate ion channel activity. fray regulation of dendrite morphology is mediated by epidermal Wingless (Wg) signaling and neuronal expression of the Wg receptor, Frizzled (Fz). How fray controls dendrite branching in class IV da neurons remains unclear, but its role in regulating morphology may depend on Wg target dishevelled (dsh).
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Type of Material: Academic dissertations (Ph.D.)
Language: en
Appears in Collections:Molecular Biology

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