EphB forward signaling controls directional branch extension and arborization required for dorsal-ventral retinotopic mapping

Neuron. 2002 Aug 1;35(3):475-87. doi: 10.1016/s0896-6273(02)00799-7.


We report that EphB receptors direct unique axonal behaviors required for mapping the dorsal-ventral (D-V) retinal axis along the lateral-medial (L-M) axis of the superior colliculus (SC). EphBs are expressed in a D-V gradient, ephrin-B1 in a L-M gradient in SC, and ephrin-B3 at its midline. EphBs and ephrin-Bs are expressed in countergradients in retina and SC. Developmental analyses reveal that retinal axons lack D-V ordering along the L-M axis, but directionally extend branches along it to establish ordered arbors. Directed branch extension is disrupted in EphB2; EphB3-deficient mice resulting in lateral ectopic arbors. Mice with kinase-inactive EphB2 have similar D-V mapping defects indicating that forward signaling dominates over reverse signaling. Our data suggest that branches of EphB expressing axons are attracted medially by ephrin-B1, and provide molecular mechanisms for D-V mapping in visual centers.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Body Patterning / genetics*
  • Brain Mapping
  • Cell Communication / physiology
  • Cell Differentiation / genetics*
  • Ephrin-B1
  • Ephrin-B2
  • Ephrin-B3
  • Functional Laterality / genetics
  • Gene Expression Regulation, Developmental / physiology
  • Growth Cones / metabolism*
  • Growth Cones / ultrastructure
  • Membrane Proteins / deficiency
  • Membrane Proteins / genetics
  • Mice
  • Mice, Knockout / abnormalities
  • Mice, Knockout / metabolism*
  • Receptor Protein-Tyrosine Kinases / genetics
  • Receptor Protein-Tyrosine Kinases / metabolism*
  • Receptors, Eph Family
  • Retina / abnormalities
  • Retina / cytology
  • Retina / metabolism*
  • Signal Transduction / physiology
  • Superior Colliculi / abnormalities
  • Superior Colliculi / cytology
  • Superior Colliculi / metabolism*
  • Visual Pathways / abnormalities
  • Visual Pathways / cytology
  • Visual Pathways / metabolism*


  • Ephrin-B1
  • Ephrin-B2
  • Ephrin-B3
  • Membrane Proteins
  • Receptor Protein-Tyrosine Kinases
  • Receptors, Eph Family