EphA5 and ephrin-A2 expression during optic nerve regeneration: a 'two-edged sword'.
During development, gradients of EphA receptors (nasal(low)-temporal(high)) and their ligands ephrin-As (rostral(low)-caudal(high)) are involved in establishing topography between retinal ganglion cells (RGCs) and the superior colliculus (SC). EphA5-expressing RGC axons are repulsed by ephrin-A2-expressing SC neurones. In adult rats RGCs maintain graded EphA5 expression but ephrin-A2 expression is down-regulated in the SC to a weak gradient. At 1 month after optic nerve transection, EphA5 expression is reduced in the few remaining RGCs and is no longer graded; by contrast, SC ephrin-A2 is up-regulated to a rostral(low)-caudal(high) gradient. Here we examined expression in adult rat 1 month after bridging the retina and SC with a peripheral nerve graft, a procedure that enhances RGC survival and permits RGC axon regeneration. Double labelling with cell markers revealed preservation of a nasal(low)-temporal(high) EphA5 gradient in RGCs and establishment of a rostral(low)-caudal(high) ephrin-A2 gradient within neurones of the SC. The results suggest a potential for guidance cues to restore the topography of RGC axons in the SC. However, high ephrin-A2 levels were also found in astrocytes surrounding the peripheral nerve graft insertion site. The repulsive ephrin-A2 environment offers at least a partial explanation for the observation that only a limited number of RGC axons can exit the graft to enter target central nervous system tissue.
Symonds
A C E
AC
School of Animal Biology M092, The University of Western Australia, 35 Stirling Highway, Crawley, Perth 6009, Western Australia.
King
C E
CE
Bartlett
C A
CA
Sauvé
Y
Y
Lund
R D
RD
Beazley
L D
LD
Dunlop
S A
SA
Rodger
J
J
D000818:Animals; D001369:Axons / Q000502:physiology; D019771:Axotomy; D002470:Cell Survival / Q000502:physiology; D036383:Ephrin-A2 / Q000235:genetics* / Q000378:metabolism; D036386:Ephrin-A5 / Q000235:genetics* / Q000378:metabolism; D005260:Female; D015870:Gene Expression / Q000502:physiology; D009416:Nerve Regeneration / Q000502:physiology*; D009900:Optic Nerve / Q000166:cytology / Q000502:physiology*; D051381:Rats; D011919:Rats, Inbred Strains; D012165:Retinal Ganglion Cells / Q000502:physiology / Q000648:ultrastructure; D012584:Sciatic Nerve / Q000166:cytology / Q000637:transplantation*; D013477:Superior Colliculi / Q000166:cytology / Q000502:physiology; D014795:Visual Pathways
D036383:Ephrin-A2; D036386:Ephrin-A5