Forward signaling by EphB1/EphB2 interacting with ephrin-B ligands at the optic chiasm is required to form the ipsilateral projection

George Chenaux, Mark Henkemeyer

Research output: Contribution to journalArticle

23 Citations (Scopus)

Abstract

EphB receptor tyrosine kinases direct axonal pathfinding through interactions with ephrin-B proteins following axon-cell contact. As EphB:ephrin-B binding leads to bidirectional signals, the contributions of signaling into the Eph-expressing cell (forward signaling) or the ephrin-expressing cell (reverse signaling) cannot be assigned using traditional protein null alleles. To determine if EphB1 is functioning solely as a receptor during axon pathfinding, a new knock-in mutant mouse was created, EphB1 T-lacZ, which expresses an intracellular-truncated EphB1-β-gal fusion protein from the endogenous locus. As in the EphB1 -/- protein null animals, the EphB1 T-lacZ/T-lacZ homozygotes fail to form the ipsilateral projecting subpopulation of retinal ganglion cell axons. This indicates that reverse signaling through the extracellular domain of EphB1 is not required for proper axon pathfinding of retinal axons at the optic chiasm. Further analysis of other EphB and ephrin-B mutant mice shows that EphB1 is the preferred receptor of ephrin-B2 and, to a lesser degree, ephrin-B1 in mediating axon guidance at the optic chiasm despite the coexpression of EphB2 in the same ipsilaterally projecting retinal axons.

Original languageEnglish (US)
Pages (from-to)1620-1633
Number of pages14
JournalEuropean Journal of Neuroscience
Volume34
Issue number10
DOIs
StatePublished - Nov 2011

Fingerprint

Ephrins
Optic Chiasm
Axons
Ligands
Ephrin-B1
Ephrin-B2
Eph Family Receptors
Proteins
Retinal Ganglion Cells
Homozygote
Protein-Tyrosine Kinases
Alleles
Axon Guidance

Keywords

  • Axon guidance
  • Binocular vision
  • EphB receptor
  • Ephrin-B ligand
  • Mouse

ASJC Scopus subject areas

  • Neuroscience(all)

Cite this

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abstract = "EphB receptor tyrosine kinases direct axonal pathfinding through interactions with ephrin-B proteins following axon-cell contact. As EphB:ephrin-B binding leads to bidirectional signals, the contributions of signaling into the Eph-expressing cell (forward signaling) or the ephrin-expressing cell (reverse signaling) cannot be assigned using traditional protein null alleles. To determine if EphB1 is functioning solely as a receptor during axon pathfinding, a new knock-in mutant mouse was created, EphB1 T-lacZ, which expresses an intracellular-truncated EphB1-β-gal fusion protein from the endogenous locus. As in the EphB1 -/- protein null animals, the EphB1 T-lacZ/T-lacZ homozygotes fail to form the ipsilateral projecting subpopulation of retinal ganglion cell axons. This indicates that reverse signaling through the extracellular domain of EphB1 is not required for proper axon pathfinding of retinal axons at the optic chiasm. Further analysis of other EphB and ephrin-B mutant mice shows that EphB1 is the preferred receptor of ephrin-B2 and, to a lesser degree, ephrin-B1 in mediating axon guidance at the optic chiasm despite the coexpression of EphB2 in the same ipsilaterally projecting retinal axons.",
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