Gradients of Eph-A6 expression in primate retina suggest roles in both vascular and axon guidance

Kozulin, Peter, Natoli, Riccardo, Madigan, Michele C., O'Brien, Keely M. Bumsted and Provis, Jan M. (2009) Gradients of Eph-A6 expression in primate retina suggest roles in both vascular and axon guidance. Molecular Vision, 15 282: 2649-2662.

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Author Kozulin, Peter
Natoli, Riccardo
Madigan, Michele C.
O'Brien, Keely M. Bumsted
Provis, Jan M.
Title Gradients of Eph-A6 expression in primate retina suggest roles in both vascular and axon guidance
Journal name Molecular Vision   Check publisher's open access policy
ISSN 1090-0535
Publication date 2009-12
Sub-type Article (original research)
Open Access Status File (Publisher version)
Volume 15
Issue 282
Start page 2649
End page 2662
Total pages 14
Place of publication Atlanta, United States
Publisher Molecular Vision
Language eng
Formatted abstract
Recently we identified high levels of expression of Eph-A6 in the macula of developing human retina and showed localization of Eph-A6 to ganglion cells (GC). In the present study we investigated the expression of some members of the ephrin family in developing primate retina, including the topography of Eph-A6 expression, and its ligands, in developing macaque retinas.

We extracted RNA from human fetal retinas and probed for Eph-A5–A7, Eph-B1, ephrin-B2, and ephrin-A1-A5 by RT–PCR, then prepared riboprobes for Eph-A5-A7, Eph-B1 and ephrin-A1, -A4 and -B2. Paraffin sections of fetal macaque retinas were used to localize expression of Ephs and ephrins by in situ hybridization and immunohistochemistry.

We identified prominent gradients of Eph-A6 mRNA expression in the ganglion cell layer (GCL) of fetal macaque retinas of different ages. The gradient of Eph-A6 expression was high near the optic disc and low at the developing macula at fetal day (Fd) 55. At Fd 70 and 80, the gradient of Eph-A6 expression was reversed, being higher temporal to the macula, and low at the disc. By Fd 110, when the fovea begins to form, a pattern of expression was established that persisted into the postnatal period, in which the highest levels of expression were detected at the developing fovea, and progressively lower levels of expression were detected at increasing distance from the fovea. Beginning at Fd 70, we also detected a gradient of Eph-A6 expression running perpendicular to the retinal surface within the GCL of central retina that was high in the inner GCL and low in the outer GCL. This second pattern persisted into the neonatal period. We found the two ligands for Eph-A6, ephrin-A1 and ephrin-A4, expressed by Pax2-immunoreactive astrocytes, in the optic nerve head and in the retina, by in situ hybridization and immunohistochemistry. We propose that during development of the retinal vasculature, migration of ligand-bearing astrocytes is slowed along this Eph-A6 expression gradient through repellent Eph-A6 - ephrin-A1 and -A4 signaling.

Patterns of Eph-A6 expression in the developing macaque retina suggest that Eph-A6 - ephrin-A1 and -A4 repellent signaling has a role in retinal vascular patterning, and in the postnatal maintenance of projections from macular and foveal GC.
Keyword Retinotopic map refinement
Lateral geniculate-nucleus
Receptor tyrosine kinase
Ganglion-cell axons
Q-Index Code C1
Q-Index Status Provisional Code
Institutional Status Non-UQ

Document type: Journal Article
Sub-type: Article (original research)
Collection: Queensland Brain Institute Publications
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