Regulation of cortical dendrite development by Slit-Robo interactions

Neuron. 2002 Jan 3;33(1):47-61. doi: 10.1016/s0896-6273(01)00566-9.

Abstract

Slit proteins have previously been shown to regulate axon guidance, branching, and neural migration. Here we report that, in addition to acting as a chemorepellant for cortical axons, Slit1 regulates dendritic development. Slit1 is expressed in the developing cortex, and exposure to Slit1 leads to increased dendritic growth and branching. Conversely, inhibition of Slit-Robo interactions by Robo-Fc fusion proteins or by a dominant-negative Robo attenuates dendritic branching. Stimulation of neurons transfected with a Met-Robo chimeric receptor with Hepatocyte growth factor leads to a robust induction of dendritic growth and branching, suggesting that Robo-mediated signaling is sufficient to induce dendritic remodeling. These experiments indicate that Slit-Robo interactions may exert a significant influence over the specification of cortical neuron morphology by regulating both axon guidance and dendritic patterning.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Cell Communication / physiology*
  • Cell Differentiation / physiology*
  • Cells, Cultured
  • Cerebral Cortex / cytology
  • Cerebral Cortex / embryology*
  • Cerebral Cortex / metabolism
  • Chemotaxis / genetics*
  • Dendrites / metabolism*
  • Dendrites / ultrastructure
  • Fetus
  • Gene Expression Regulation, Developmental / physiology
  • Intercellular Signaling Peptides and Proteins
  • Membrane Proteins / genetics
  • Membrane Proteins / metabolism
  • Mice
  • Nerve Tissue Proteins / genetics
  • Nerve Tissue Proteins / metabolism*
  • Peptide Fragments / genetics
  • Peptide Fragments / metabolism
  • Protein Structure, Tertiary / physiology
  • Rats
  • Rats, Long-Evans
  • Receptors, Immunologic / genetics
  • Receptors, Immunologic / metabolism*
  • Signal Transduction / genetics
  • Transfection

Substances

  • Intercellular Signaling Peptides and Proteins
  • Membrane Proteins
  • Nerve Tissue Proteins
  • Peptide Fragments
  • Receptors, Immunologic
  • Robo2 protein, mouse
  • Slit1 protein, mouse
  • Slit1 protein, rat
  • Slit3 protein, mouse
  • Slit3 protein, rat
  • roundabout protein
  • Slit homolog 2 protein