Dscam expression levels determine presynaptic arbor sizes in Drosophila sensory neurons

Neuron. 2013 Jun 5;78(5):827-38. doi: 10.1016/j.neuron.2013.05.020.

Abstract

Expression of the Down syndrome cell-adhesion molecule (Dscam) is increased in the brains of patients with several neurological disorders. Although Dscam is critically involved in many aspects of neuronal development, little is known about either the mechanism that regulates its expression or the functional consequences of dysregulated Dscam expression. Here, we show that Dscam expression levels serve as an instructive code for the size control of presynaptic arbor. Two convergent pathways, involving dual leucine zipper kinase (DLK) and fragile X mental retardation protein (FMRP), control Dscam expression through protein translation. Defects in this regulation of Dscam translation lead to exuberant presynaptic arbor growth in Drosophila somatosensory neurons. Our findings uncover a function of Dscam in presynaptic size control and provide insights into how dysregulated Dscam may contribute to the pathogenesis of neurological disorders.

Publication types

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

MeSH terms

  • Animals
  • Animals, Genetically Modified
  • Cell Adhesion Molecules / genetics
  • Cell Adhesion Molecules / metabolism*
  • Cell Line, Transformed
  • Drosophila
  • Drosophila Proteins / genetics
  • Drosophila Proteins / metabolism*
  • Embryo, Nonmammalian
  • Fragile X Mental Retardation Protein / metabolism
  • Functional Laterality
  • Gene Expression Regulation, Developmental / genetics
  • Gene Expression Regulation, Developmental / physiology*
  • Green Fluorescent Proteins / genetics
  • Green Fluorescent Proteins / metabolism
  • Immunoprecipitation
  • MAP Kinase Kinase Kinases / metabolism
  • Presynaptic Terminals / physiology*
  • RNA, Messenger / metabolism
  • Sensory Receptor Cells / cytology*
  • Signal Transduction / genetics
  • Statistics, Nonparametric
  • Transfection

Substances

  • Cell Adhesion Molecules
  • Drosophila Proteins
  • Dscam1 protein, Drosophila
  • RNA, Messenger
  • Fragile X Mental Retardation Protein
  • Green Fluorescent Proteins
  • MAP Kinase Kinase Kinases
  • mitogen-activated protein kinase kinase kinase 12