Epidermis-Derived Semaphorin Promotes Dendrite Self-Avoidance by Regulating Dendrite-Substrate Adhesion in Drosophila Sensory Neurons

Neuron. 2016 Feb 17;89(4):741-55. doi: 10.1016/j.neuron.2016.01.020. Epub 2016 Feb 4.

Abstract

Precise patterning of dendritic arbors is critical for the wiring and function of neural circuits. Dendrite-extracellular matrix (ECM) adhesion ensures that the dendrites of Drosophila dendritic arborization (da) sensory neurons are properly restricted in a 2D space, and thereby facilitates contact-mediated dendritic self-avoidance and tiling. However, the mechanisms regulating dendrite-ECM adhesion in vivo are poorly understood. Here, we show that mutations in the semaphorin ligand sema-2b lead to a dramatic increase in self-crossing of dendrites due to defects in dendrite-ECM adhesion, resulting in a failure to confine dendrites to a 2D plane. Furthermore, we find that Sema-2b is secreted from the epidermis and signals through the Plexin B receptor in neighboring neurons. Importantly, we find that Sema-2b/PlexB genetically and physically interacts with TORC2 complex, Tricornered (Trc) kinase, and integrins. These results reveal a novel role for semaphorins in dendrite patterning and illustrate how epidermal-derived cues regulate neural circuit assembly.

Publication types

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

MeSH terms

  • Animals
  • Animals, Genetically Modified
  • Cell Communication
  • Dendrites / physiology*
  • Drosophila
  • Drosophila Proteins / genetics
  • Drosophila Proteins / metabolism*
  • Epidermis / physiology*
  • Focal Adhesion Kinase 1 / genetics
  • Focal Adhesion Kinase 1 / metabolism*
  • Gene Expression Regulation, Developmental / genetics*
  • Green Fluorescent Proteins / genetics
  • Green Fluorescent Proteins / metabolism
  • Immunoprecipitation
  • Larva
  • Mechanistic Target of Rapamycin Complex 2
  • Molecular Biology
  • Multiprotein Complexes / metabolism
  • Mutation / genetics
  • Nerve Tissue Proteins / genetics
  • Nerve Tissue Proteins / metabolism
  • Receptors, Cell Surface / genetics
  • Receptors, Cell Surface / metabolism
  • Semaphorins / genetics
  • Semaphorins / metabolism*
  • Sensory Receptor Cells / cytology*
  • TOR Serine-Threonine Kinases / metabolism
  • Transfection

Substances

  • Drosophila Proteins
  • Multiprotein Complexes
  • Nerve Tissue Proteins
  • Receptors, Cell Surface
  • Semaphorins
  • plexB protein, Drosophila
  • Green Fluorescent Proteins
  • TOR Serine-Threonine Kinases
  • Fak protein, Drosophila
  • Focal Adhesion Kinase 1
  • Mechanistic Target of Rapamycin Complex 2