MicroRNA processing pathway regulates olfactory neuron morphogenesis.
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.
Berdnik
Daniela
D
Howard Hughes Medical Institute, Department of Biology, Stanford University, Stanford, CA 94305, USA.
Fan
Audrey P
AP
Potter
Christopher J
CJ
Luo
Liqun
L
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
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