title: MicroRNA processing pathway regulates olfactory neuron morphogenesis.
abstract: The microRNA (miRNA) processing pathway produces miRNAs as posttranscriptional regulators of gene expression. The nuclear RNase III Drosha catalyzes the first processing step together with the dsRNA binding protein DGCR8/Pasha generating pre-miRNAs [1, 2]. The next cleavage employs the cytoplasmic RNase III Dicer producing miRNA duplexes [3, 4]. Finally, Argonautes are recruited with miRNAs into an RNA-induced silencing complex for mRNA recognition (Figure 1A). Here, we identify two members of the miRNA pathway, Pasha and Dicer-1, in a forward genetic screen for mutations that disrupt wiring specificity of Drosophila olfactory projection neurons (PNs). The olfactory system is built as discrete map of highly stereotyped neuronal connections [5, 6]. Each PN targets dendrites to a specific glomerulus in the antennal lobe and projects axons stereotypically into higher brain centers [7-9]. In selected PN classes, pasha and Dicer-1 mutants cause specific PN dendrite mistargeting in the antennal lobe and altered axonal terminations in higher brain centers. Furthermore, Pasha and Dicer-1 act cell autonomously in postmitotic neurons to regulate dendrite and axon targeting during development. However, Argonaute-1 and Argonaute-2 are dispensable for PN morphogenesis. Our findings suggest a role for the miRNA processing pathway in establishing wiring specificity in the nervous system.
authors.affiliation: Howard Hughes Medical Institute, Department of Biology, Stanford University, Stanford, CA 94305, USA.
authors.forename: Daniela
authors.initials: D
authors.lastname: Berdnik
authors.forename: Audrey P
authors.initials: AP
authors.lastname: Fan
authors.forename: Christopher J
authors.initials: CJ
authors.lastname: Potter
authors.forename: Liqun
authors.initials: L
authors.lastname: Luo
mesh_terms: D000818:Animals; D060565:Argonaute Proteins; D049108:Cell Enlargement; D003712:Dendrites / Q000378:metabolism / Q000648:ultrastructure; D004330:Drosophila / Q000166:cytology* / Q000196:embryology / Q000235:genetics / Q000378:metabolism; D029721:Drosophila Proteins / Q000235:genetics / Q000378:metabolism / Q000502:physiology; D039642:Eukaryotic Initiation Factors; D005786:Gene Expression Regulation; D035683:MicroRNAs / Q000378:metabolism* / Q000502:physiology; D008954:Models, Biological; D009154:Mutation; D009475:Neurons, Afferent / Q000166:cytology*; D017729:Presynaptic Terminals / Q000378:metabolism / Q000648:ultrastructure; D020365:RNA Helicases / Q000235:genetics / Q000378:metabolism / Q000502:physiology; D016601:RNA-Binding Proteins / Q000235:genetics / Q000378:metabolism / Q000502:physiology; D034743:RNA-Induced Silencing Complex / Q000235:genetics; D043244:Ribonuclease III
chemical_list: C489654:AGO1 protein, Drosophila; C433807:AGO2 protein, Drosophila; D060565:Argonaute Proteins; D029721:Drosophila Proteins; D039642:Eukaryotic Initiation Factors; D035683:MicroRNAs; C534610:Pasha protein, Drosophila; D016601:RNA-Binding Proteins; D034743:RNA-Induced Silencing Complex; C515033:Dcr-1 protein, Drosophila; D043244:Ribonuclease III; D020365:RNA Helicases