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.
Bibliographical noteFunding Information:
We are very grateful to Rachel Wong, Josh Sanes, Paul Bridgeman, Andreas Burkhalter and Brad Miller for experimental advice and assistance. We also recognize Joseph Mertz, Sylvia Johnson, Doug Cox and Alex Barsam for technical support. Mouse colony maintenance was managed with care by the technicians of the Washington University Animal Facility. This research was supported by the Horncrest Foundation, McDonnell Center for Higher Brain Function, and Knights Templar Foundation Awards to S.M.C. and by the Keck Foundation and NIH (DA020812) to A.D.
- Retinal activity