MicroRNA processing pathway regulates olfactory neuron morphogenesis

Curr Biol. 2008 Nov 25;18(22):1754-9. doi: 10.1016/j.cub.2008.09.045. Epub 2008 Nov 13.

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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Argonaute Proteins
  • Cell Enlargement
  • Dendrites / metabolism
  • Dendrites / ultrastructure
  • Drosophila / cytology*
  • Drosophila / embryology
  • Drosophila / genetics
  • Drosophila / metabolism
  • Drosophila Proteins / genetics
  • Drosophila Proteins / metabolism
  • Drosophila Proteins / physiology
  • Eukaryotic Initiation Factors
  • Gene Expression Regulation
  • MicroRNAs / metabolism*
  • MicroRNAs / physiology
  • Models, Biological
  • Mutation
  • Neurons, Afferent / cytology*
  • Presynaptic Terminals / metabolism
  • Presynaptic Terminals / ultrastructure
  • RNA Helicases / genetics
  • RNA Helicases / metabolism
  • RNA Helicases / physiology
  • RNA-Binding Proteins / genetics
  • RNA-Binding Proteins / metabolism
  • RNA-Binding Proteins / physiology
  • RNA-Induced Silencing Complex / genetics
  • Ribonuclease III

Substances

  • AGO1 protein, Drosophila
  • AGO2 protein, Drosophila
  • Argonaute Proteins
  • Drosophila Proteins
  • Eukaryotic Initiation Factors
  • MicroRNAs
  • Pasha protein, Drosophila
  • RNA-Binding Proteins
  • RNA-Induced Silencing Complex
  • Dcr-1 protein, Drosophila
  • Ribonuclease III
  • RNA Helicases