Regulation of retinal axon growth by secreted Vax1 homeodomain protein

Elife. 2014 Sep 8;3:e02671. doi: 10.7554/eLife.02671.

Abstract

Retinal ganglion cell (RGC) axons of binocular animals cross the midline at the optic chiasm (OC) to grow toward their synaptic targets in the contralateral brain. Ventral anterior homeobox 1 (Vax1) plays an essential role in the development of the OC by regulating RGC axon growth in a non-cell autonomous manner. In this study, we identify an unexpected function of Vax1 that is secreted from ventral hypothalamic cells and diffuses to RGC axons, where it promotes axonal growth independent of its transcription factor activity. We demonstrate that Vax1 binds to extracellular sugar groups of the heparan sulfate proteoglycans (HSPGs) located in RGC axons. Both Vax1 binding to HSPGs and subsequent penetration into the axoplasm, where Vax1 activates local protein synthesis, are required for RGC axonal growth. Together, our findings demonstrate that Vax1 possesses a novel RGC axon growth factor activity that is critical for the development of the mammalian binocular visual system.

Keywords: developmental biology; intercellular protein transfer; mouse; neuroscience; optic chiasm; retinal axon growth; stem cells; ventral anterior homeobox 1 (Vax1).

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Axons / metabolism*
  • Drosophila melanogaster / metabolism
  • Extracellular Space / metabolism
  • Heparan Sulfate Proteoglycans / metabolism
  • Homeodomain Proteins / metabolism*
  • Imaginal Discs / metabolism
  • Intercellular Signaling Peptides and Proteins / metabolism
  • Mice
  • Models, Biological
  • Neuropeptides / metabolism*
  • Protein Binding
  • Protein Biosynthesis
  • Retinal Ganglion Cells / metabolism*
  • Time-Lapse Imaging
  • Wings, Animal / metabolism

Substances

  • Heparan Sulfate Proteoglycans
  • Homeodomain Proteins
  • Intercellular Signaling Peptides and Proteins
  • Neuropeptides
  • Vax1 protein, mouse

Grant support

The funder had no role in study design, data collection and interpretation, or the decision to submit the work for publication.