title: Forward signaling by EphB1/EphB2 interacting with ephrin-B ligands at the optic chiasm is required to form the ipsilateral projection.
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.
authors: Department of Developmental Biology and Kent Waldrep Foundation Center for Basic Research on Nerve Growth and Regeneration, University of Texas Southwestern Medical Center, 6000 Harry Hines Boulevard, Dallas, TX 75390-9133, USA.
authors: George
authors: G
authors: Chenaux
authors: Mark
authors: M
authors: Henkemeyer
mesh_terms: D000818:Animals; D002450:Cell Communication / Q000502:physiology*; D002465:Cell Movement / Q000502:physiology; D036387:Ephrin-B1 / Q000235:genetics / Q000378:metabolism*; D036388:Ephrin-B2 / Q000235:genetics / Q000378:metabolism*; D005260:Female; D005829:Geniculate Bodies / Q000166:cytology / Q000378:metabolism; D006801:Humans; D008024:Ligands; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D009897:Optic Chiasm / Q000033:anatomy & histology* / Q000502:physiology*; D009900:Optic Nerve / Q000378:metabolism; D036225:Receptor, EphB1 / Q000235:genetics / Q000378:metabolism; D036183:Receptor, EphB2 / Q000235:genetics / Q000378:metabolism*; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000378:metabolism; D012160:Retina / Q000378:metabolism; D012165:Retinal Ganglion Cells / Q000502:physiology; D015398:Signal Transduction / Q000502:physiology; D014795:Visual Pathways / Q000033:anatomy & histology / Q000196:embryology
chemical_list: D036387:Ephrin-B1; D036388:Ephrin-B2; D008024:Ligands; D011993:Recombinant Fusion Proteins; D036225:Receptor, EphB1; D036183:Receptor, EphB2