GAP-43 mediates retinal axon interaction with lateral diencephalon cells during optic tract formation.
GAP-43 is an abundant intracellular growth cone protein that can serve as a PKC substrate and regulate calmodulin availability. In mice with targeted disruption of the GAP-43 gene, retinal ganglion cell (RGC) axons fail to progress normally from the optic chiasm into the optic tracts. The underlying cause is unknown but, in principle, can result from either the disruption of guidance mechanisms that mediate axon exit from the midline chiasm region or defects in growth cone signaling required for entry into the lateral diencephalic wall to form the optic tracts. Results here show that, compared to wild-type RGC axons, GAP-43-deficient axons exhibit reduced growth in the presence of lateral diencephalon cell membranes. Reduced growth is not observed when GAP-43-deficient axons are cultured with optic chiasm, cortical, or dorsal midbrain cells. Lateral diencephalon cell conditioned medium inhibits growth of both wild-type and GAP-43-deficient axons to a similar extent and does not affect GAP-43-deficient axons more so. Removal or transplant replacement of the lateral diencephalon optic tract entry zone in GAP-43-deficient embryo preparations results in robust RGC axon exit from the chiasm. Together these data show that RGC axon exit from the midline region does not require GAP-43 function. Instead, GAP-43 appears to mediate RGC axon interaction with guidance cues in the lateral diencephalic wall, suggesting possible involvement of PKC and calmodulin signaling during optic tract formation.
Zhang
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Beckman Vision Center, Neuroscience and Biomedical Sciences Programs, Departments of Ophthalmology & Physiology, University of California, San Francisco, USA.
Lu
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Severin
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Sretavan
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DW
D000818:Animals; D001369:Axons / Q000502:physiology*; D002462:Cell Membrane / Q000502:physiology; D002478:Cells, Cultured; D017077:Culture Media, Conditioned; D004027:Diencephalon / Q000166:cytology / Q000196:embryology*; D005091:Exons; D016332:Fetal Tissue Transplantation / Q000502:physiology; D019922:GAP-43 Protein / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D007031:Hypothalamus / Q000196:embryology; D051379:Mice; D018345:Mice, Knockout; D016501:Neurites / Q000502:physiology; D009474:Neurons / Q000166:cytology / Q000502:physiology*; D009897:Optic Chiasm / Q000196:embryology*; D012160:Retina / Q000166:cytology / Q000196:embryology* / Q000637:transplantation; D012165:Retinal Ganglion Cells / Q000502:physiology*; D017384:Sequence Deletion; D015398:Signal Transduction; D014795:Visual Pathways / Q000166:cytology / Q000196:embryology*
D017077:Culture Media, Conditioned; D019922:GAP-43 Protein