AL-1-induced growth cone collapse of rat cortical neurons is correlated with REK7 expression and rearrangement of the actin cytoskeleton

Eur J Neurosci. 1997 Jan;9(1):177-88. doi: 10.1111/j.1460-9568.1997.tb01365.x.


Previous experiments identified AL-1 as a glycosylphosphatidylinositol (GPI)-linked ligand for the Eph-related receptor, REK7, and showed that a REK7-IgG fusion protein blocks axon bundling in co-cultures of cortical neurons on astrocytes, suggesting a role for REK7 and AL-1 in axon fasciculation. Subsequent identification of RAGS, the chick homologue of AL-1, as a repellent axon guidance molecule in the developing chick visual system led to speculation that AL-1, expressed on astrocytes, provides a repellent stimulus for cortical axons, inducing them to bundle as an avoidance mechanism. Using a growth cone collapse assay to test this hypothesis, we show that a soluble AL-1-IgG fusion protein is a potent collapsing factor for embryonic rat cortical neurons. The response is strongly correlated with REK7 expression, implicating REK7 as a receptor mediating AL-1-induced collapse. Morphological collapse is preceded by an AL-1-IgG-induced reorganization of the actin cytoskeleton that resembles the effects of cytochalasin D. This suggests a pathway whereby REK7 activation by AL-1 leads to perturbation of the actin cytoskeleton, possibly by an effect on actin polymerization, followed by growth cone collapse. We further show that AL-1-IgG causes collapse of rat hippocampal neurons and rat retinal ganglion cells. These data suggest a role for REK7 and AL-1 in the patterning of axonal connections in the developing cortex, hippocampus and visual system.

MeSH terms

  • Actins / biosynthesis*
  • Animals
  • CD4 Antigens / metabolism
  • Cerebral Cortex / drug effects
  • Cerebral Cortex / growth & development*
  • Cerebral Cortex / metabolism
  • Cytoskeleton / drug effects
  • Cytoskeleton / metabolism*
  • Ephrin-A2
  • Fluorescent Antibody Technique, Indirect
  • Glycosylphosphatidylinositols / pharmacology
  • Histocytochemistry
  • Ligands
  • Neurons / drug effects
  • Neurons / metabolism*
  • Neurons / physiology*
  • Rats
  • Receptor Protein-Tyrosine Kinases / biosynthesis*
  • Receptor Protein-Tyrosine Kinases / genetics
  • Retina / cytology
  • Rhodamines
  • Transcription Factors / pharmacology*
  • Visual Cortex / cytology
  • Visual Cortex / growth & development


  • Actins
  • CD4 Antigens
  • Ephrin-A2
  • Glycosylphosphatidylinositols
  • Ligands
  • Rhodamines
  • Transcription Factors
  • Receptor Protein-Tyrosine Kinases