Phr1 regulates retinogeniculate targeting independent of activity and ephrin-A signalling.
Proper functioning of the mammalian visual system requires that connections between the eyes and their central targets develop precisely. At birth, axons from the two eyes project to broad, overlapping regions of the dorsal-lateral geniculate nucleus (dLGN). In the adult, retinal axons segregate into distinct monocular regions at stereotyped locations within the dLGN. This process is driven by both molecular cues and activity-dependent synaptic competition. Here we demonstrate that Phr1, an evolutionarily conserved regulator of synapse formation and axon guidance, defines a novel molecular pathway required for proper localization of retinogeniculate projections. Following conditional excision of Phr1 in the retina, eye-specific domains within the dLGN are severely disturbed, despite normal spontaneous retinal wave activity and monocular segregation. Although layer placement is dramatically altered, Phr1 mutant retinal axons respond to ephrin-A in vitro. These findings indicate that Phr1 is a key presynaptic regulator of retinogeniculate layer placement independent of activity, segregation, or ephrin-A signaling.
Department of Ophthalmology and Visual Sciences, Washington University School of Medicine, St. Louis, MO 63110, USA.
Susan M
SM
Culican
A Joseph
AJ
Bloom
Joshua A
JA
Weiner
Aaron
A
DiAntonio
D000818:Animals; D001369:Axons / Q000378:metabolism / Q000473:pathology; D036342:Ephrins / Q000378:metabolism*; D005829:Geniculate Bodies / Q000002:abnormalities / Q000378:metabolism*; D047908:Intracellular Signaling Peptides and Proteins / Q000172:deficiency*; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D018345:Mice, Knockout; D009897:Optic Chiasm / Q000196:embryology / Q000378:metabolism; D012160:Retina / Q000196:embryology / Q000473:pathology / Q000502:physiology*; D015398:Signal Transduction; D014795:Visual Pathways / Q000002:abnormalities / Q000378:metabolism
D036342:Ephrins; D047908:Intracellular Signaling Peptides and Proteins; D008565:Membrane Proteins; C485943:Plekhb1 protein, mouse