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Phr1 regulates retinogeniculate targeting independent of activity and ephrin-A signalling
Journal article   Open access   Peer reviewed

Phr1 regulates retinogeniculate targeting independent of activity and ephrin-A signalling

Susan M Culican, A Joseph Bloom, Joshua A Weiner and Aaron DiAntonio
Molecular and cellular neurosciences, Vol.41(3), pp.304-312
07/2009
DOI: 10.1016/j.mcn.2009.04.001
PMCID: PMC2697264
PMID: 19371781

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Abstract

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.
Visual Pathways - abnormalities Optic Chiasm - embryology Signal Transduction Membrane Proteins - genetics Geniculate Bodies - metabolism Visual Pathways - metabolism Axons - metabolism Optic Chiasm - metabolism Retina - embryology Mice, Knockout Geniculate Bodies - abnormalities Intracellular Signaling Peptides and Proteins - deficiency Retina - physiology Animals Axons - pathology Ephrins - metabolism Membrane Proteins - metabolism Mice Retina - pathology

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