Extracellular Engrailed participates in the topographic guidance of retinal axons in vivo

Neuron. 2009 Nov 12;64(3):355-366. doi: 10.1016/j.neuron.2009.09.018.


Engrailed transcription factors regulate the expression of guidance cues that pattern retinal axon terminals in the dorsal midbrain. They also act directly to guide axon growth in vitro. We show here that an extracellular En gradient exists in the tectum along the anterior-posterior axis. Neutralizing extracellular Engrailed in vivo with antibodies expressed in the tectum causes temporal axons to map aberrantly to the posterior tectum in chick and Xenopus. Furthermore, posterior membranes from wild-type tecta incubated with anti-Engrailed antibodies or posterior membranes from Engrailed-1 knockout mice exhibit diminished repulsive activity for temporal axons. Since EphrinAs play a major role in anterior-posterior mapping, we tested whether Engrailed cooperates with EphrinA5 in vitro. We find that Engrailed restores full repulsion to axons given subthreshold doses of EphrinA5. Collectively, our results indicate that extracellular Engrailed contributes to retinotectal mapping in vivo by modulating the sensitivity of growth cones to EphrinA.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Axons / physiology*
  • Chemotaxis / physiology*
  • Chick Embryo
  • Extracellular Space / metabolism*
  • Growth Cones / physiology
  • Homeodomain Proteins / genetics
  • Homeodomain Proteins / metabolism*
  • In Vitro Techniques
  • Mice
  • Mice, Knockout
  • Receptors, Eph Family / metabolism
  • Retina / embryology
  • Retina / growth & development
  • Retina / physiology*
  • Retinal Ganglion Cells / physiology
  • Superior Colliculi / embryology
  • Superior Colliculi / growth & development
  • Superior Colliculi / physiology*
  • Visual Pathways / embryology
  • Visual Pathways / growth & development
  • Visual Pathways / physiology
  • Xenopus


  • En1 protein, mouse
  • Homeodomain Proteins
  • Receptors, Eph Family