Modulation of EphA receptor function by coexpressed ephrinA ligands on retinal ganglion cell axons.
The Eph family is thought to exert its function through the complementary expression of receptors and ligands. Here, we show that EphA receptors colocalize on retinal ganglion cell (RGC) axons with EphA ligands, which are expressed in a high-nasal-to-low-temporal pattern. In the stripe assay, only temporal axons are normally sensitive for repellent axon guidance cues of the caudal tectum. However, overexpression of ephrinA ligands on temporal axons abolishes this sensitivity, whereas treatment with PI-PLC both removes ephrinA ligands from retinal axons and induces a striped outgrowth of formerly insensitive nasal axons. In vivo, retinal overexpression of ephrinA2 leads to topographic targeting errors of temporal axons. These data suggest that differential ligand expression on retinal axons is a major determinant of topographic targeting in the retinotectal projection.
Hornberger
M R
MR
Department of Physical Biology, Max-Planck Institute for Developmental Biology, Tübingen, Germany.
Dütting
D
D
Ciossek
T
T
Yamada
T
T
Handwerker
C
C
Lang
S
S
Weth
F
F
Huf
J
J
Wessel
R
R
Logan
C
C
Tanaka
H
H
Drescher
U
U
D000818:Animals; D001369:Axons / Q000502:physiology*; D001931:Brain Mapping; D002642:Chick Embryo; D036383:Ephrin-A2; D008024:Ligands; D009666:Nose / Q000294:innervation; D043265:Phosphatidylinositol Diacylglycerol-Lyase; D054801:Phosphoinositide Phospholipase C; D010766:Phosphorylation; D020794:Receptor Protein-Tyrosine Kinases / Q000502:physiology*; D015203:Reproducibility of Results; D012165:Retinal Ganglion Cells / Q000648:ultrastructure*; D013477:Superior Colliculi / Q000502:physiology; D014157:Transcription Factors / Q000502:physiology*; D010738:Type C Phospholipases / Q000378:metabolism; D014795:Visual Pathways / Q000502:physiology
D036383:Ephrin-A2; D008024:Ligands; D014157:Transcription Factors; D020794:Receptor Protein-Tyrosine Kinases; D010738:Type C Phospholipases; D054801:Phosphoinositide Phospholipase C; D043265:Phosphatidylinositol Diacylglycerol-Lyase