EphB forward signaling controls directional branch extension and arborization required for dorsal-ventral retinotopic mapping.
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.
Hindges
Robert
R
Molecular Neurobiology Laboratory, The Salk Institute, 10010 North Torrey Pines Road, 92037, La Jolla, CA 92037, USA.
McLaughlin
Todd
T
Genoud
Nicolas
N
Henkemeyer
Mark
M
O'Leary
Dennis  D M
D
D000818:Animals; D019521:Body Patterning / Q000235:genetics*; D001931:Brain Mapping; D002450:Cell Communication / Q000502:physiology; D002454:Cell Differentiation / Q000235:genetics*; D036387:Ephrin-B1; D036388:Ephrin-B2; D036389:Ephrin-B3; D007839:Functional Laterality / Q000235:genetics; D018507:Gene Expression Regulation, Developmental / Q000502:physiology; D020439:Growth Cones / Q000378:metabolism* / Q000648:ultrastructure; D008565:Membrane Proteins / Q000172:deficiency / Q000235:genetics; D051379:Mice; D018345:Mice, Knockout / Q000002:abnormalities / Q000378:metabolism*; D020794:Receptor Protein-Tyrosine Kinases / Q000235:genetics / Q000378:metabolism*; D036081:Receptors, Eph Family; D012160:Retina / Q000002:abnormalities / Q000166:cytology / Q000378:metabolism*; D015398:Signal Transduction / Q000502:physiology; D013477:Superior Colliculi / Q000002:abnormalities / Q000166:cytology / Q000378:metabolism*; D014795:Visual Pathways / Q000002:abnormalities / Q000166:cytology / Q000378:metabolism*
D036387:Ephrin-B1; D036388:Ephrin-B2; D036389:Ephrin-B3; D008565:Membrane Proteins; D020794:Receptor Protein-Tyrosine Kinases; D036081:Receptors, Eph Family