2- and 6-O-sulfated proteoglycans have distinct and complementary roles in cranial axon guidance and motor neuron migration

Development. 2016 Jun 1;143(11):1907-13. doi: 10.1242/dev.126854. Epub 2016 Apr 5.

Abstract

The correct migration and axon extension of neurons in the developing nervous system is essential for the appropriate wiring and function of neural networks. Here, we report that O-sulfotransferases, a class of enzymes that modify heparan sulfate proteoglycans (HSPGs), are essential to regulate neuronal migration and axon development. We show that the 6-O-sulfotransferases HS6ST1 and HS6ST2 are essential for cranial axon patterning, whilst the 2-O-sulfotransferase HS2ST (also known as HS2ST1) is important to regulate the migration of facial branchiomotor (FBM) neurons in the hindbrain. We have also investigated how HS2ST interacts with other signals in the hindbrain and show that fibroblast growth factor (FGF) signalling regulates FBM neuron migration in an HS2ST-dependent manner.

Keywords: Axon guidance; Fibroblast growth factor (FGF); Heparan sulfate proteoglycan (HSPG); Neuron migration; Sulfotransferase; Vascular endothelial growth factor (VEGF).

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Axon Guidance* / drug effects
  • Cell Movement / drug effects*
  • Fibroblast Growth Factors / pharmacology
  • Mice, Inbred C57BL
  • Motor Neurons / cytology*
  • Motor Neurons / drug effects
  • Motor Neurons / metabolism
  • Proteoglycans / metabolism*
  • Skull / drug effects
  • Skull / metabolism*
  • Sulfates / metabolism*
  • Sulfotransferases / metabolism
  • Trigeminal Ganglion / drug effects
  • Trigeminal Ganglion / metabolism
  • Vascular Endothelial Growth Factor A / pharmacology

Substances

  • Proteoglycans
  • Sulfates
  • Vascular Endothelial Growth Factor A
  • Fibroblast Growth Factors
  • Sulfotransferases