title: Ephrin-As and patterned retinal activity act together in the development of topographic maps in the primary visual system.
abstract: The development of topographic maps in the primary visual system is thought to rely on a combination of EphA/ephrin-A interactions and patterned neural activity. Here, we characterize the retinogeniculate and retinocollicular maps of mice mutant for ephrins-A2, -A3, and -A5 (the three ephrin-As expressed in the mouse visual system), mice mutant for the beta2 subunit of the nicotinic acetylcholine receptor (that lack early patterned retinal activity), and mice mutant for both ephrin-As and beta2. We also provide the first comprehensive anatomical description of the topographic connections between the retina and the dorsal lateral geniculate nucleus. We find that, although ephrin-A2/A3/A5 triple knock-out mice have severe mapping defects in both projections, they do not completely lack topography. Mice lacking beta2-dependent retinal activity have nearly normal topography but fail to refine axonal arbors. Mice mutant for both ephrin-As and beta2 have synergistic mapping defects that result in a near absence of map in the retinocollicular projection; however, the retinogeniculate projection is not as severely disrupted as the retinocollicular projection is in these mutants. These results show that ephrin-As and patterned retinal activity act together to establish topographic maps, and demonstrate that midbrain and forebrain connections have a differential requirement for ephrin-As and patterned retinal activity in topographic map development.
authors.affiliation: Department of Molecular, Cell, and Developmental Biology, University of California, Santa Cruz, Santa Cruz, California 95064, USA.
authors.forename: Cory
authors.initials: C
authors.lastname: Pfeiffenberger
authors.forename: Jena
authors.initials: J
authors.lastname: Yamada
authors.forename: David A
authors.initials: DA
authors.lastname: Feldheim
mesh_terms: D000818:Animals; D001931:Brain Mapping / Q000379:methods*; D036383:Ephrin-A2 / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology; D036386:Ephrin-A5 / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology; D036342:Ephrins / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology*; D005829:Geniculate Bodies / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D012160:Retina / Q000378:metabolism*; D014795:Visual Pathways / Q000378:metabolism*
chemical_list: D036383:Ephrin-A2; D036386:Ephrin-A5; D036342:Ephrins