Protocadherin-18b interacts with Nap1 to control motor axon growth and arborization in zebrafish

Mol Biol Cell. 2014 Mar;25(5):633-42. doi: 10.1091/mbc.E13-08-0475. Epub 2013 Dec 26.

Abstract

The proper assembly of neural circuits during development requires the precise control of axon outgrowth, guidance, and arborization. Although the protocadherin family of cell surface receptors is widely hypothesized to participate in neural circuit assembly, their specific roles in neuronal development remain largely unknown. Here we demonstrate that zebrafish pcdh18b is involved in regulating axon arborization in primary motoneurons. Although axon outgrowth and elongation appear normal, antisense morpholino knockdown of pcdh18b results in dose-dependent axon branching defects in caudal primary motoneurons. Cell transplantation experiments show that this effect is cell autonomous. Pcdh18b interacts with Nap1, a core component of the WAVE complex, through its intracellular domain, suggesting a role in the control of actin assembly. Like that of Pcdh18b, depletion of Nap1 results in reduced branching of motor axons. Time-lapse imaging and quantitative analysis of axon dynamics indicate that both Pcdh18b and Nap1 regulate axon arborization by affecting the density of filopodia along the shaft of the extending axon.

Publication types

  • Research Support, American Recovery and Reinvestment Act
  • 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
  • Axons / metabolism
  • Axons / physiology*
  • Axons / ultrastructure
  • Cadherins / metabolism
  • Cadherins / physiology*
  • Carrier Proteins / metabolism
  • Carrier Proteins / physiology*
  • Motor Neurons / metabolism
  • Motor Neurons / physiology
  • Motor Neurons / ultrastructure
  • Neurogenesis
  • Protocadherins
  • Zebrafish / metabolism*
  • Zebrafish / physiology
  • Zebrafish Proteins / metabolism
  • Zebrafish Proteins / physiology*

Substances

  • Cadherins
  • Carrier Proteins
  • Pcdh18 protein, zebrafish
  • Protocadherins
  • Zebrafish Proteins