Trends in Neurosciences
ReviewEphrin-As as receptors in topographic projections
Section snippets
The retinotectal projection
It is generally believed that topographic projections form on the basis of graded expressions of guidance molecules by the projecting axons and the target area 17, 18. The retinotectal projection is the prototypic model system to study development of topographic maps. Here, axons from the nasal retina project to the posterior tectum and those from the temporal retina project to the anterior tectum (Fig. 1). Axons from the dorsal and ventral retina project to the ventral and dorsal tectum
The vomeronasal projection
A hitherto unique expression pattern has recently been found in the vomeronasal system: ephrin-As are expressed on vomeronasal axons and EphAs are expressed in the target area [16] (Fig. 2 and Fig. 3b). The vomeronasal projection therefore provides a suitable model system for investigating the function of axonally expressed ephrin-As without any interference from axonal EphA receptor signalling.
The vomeronasal – or accessory – olfactory system detects pheromones, which control innate behaviours
Signalling pathways activated by EphAs versus those activated by ephrin-As
These studies now suggest that axonally localized EphAs and ephrin-As exert opposite functions, with activation of EphAs leading to repulsion, and activation of ephrin-As leading to increased attraction and/or adhesion of growth cones. In cases of co-expression of EphAs and ephrin-As, the read-out appears to be ‘mixed’, possibly depending on the relative expression levels of EphAs and ephrin-As (Fig. 3).
Intriguingly, these opposite behaviours can be correlated with activation of biochemical
Outlook
Anticipating that the discussed signalling pathways are functionally important in steering axonal growth cones, the Eph system could provide integrated control of key components of the motility apparatus of a growth cone. This includes actin–myosin contractility, actin assembly and disassembly, and adhesion to the extracellular matrix. Motility could be increased by activating ephrin-As and decreased by activating EphAs. If these stimuli were provided locally, the changes of growth cone
Acknowledgements
We would like to thank Sarah Guthrie, Britta Eickholt and Tahira Rashid for valuable discussions on the mamuscript.
References (62)
Molecular development of sensory maps: representing sights and smells in the brain
Cell
(1999)Topographic mapping: organising by repulsion and competition?
Curr. Biol.
(2000)Excitatory Eph receptors and adhesive ephrin ligands
Curr. Opin. Cell Biol.
(2001)- et al.
Eph receptors and ephrins in neural development
Curr. Opin. Neurobiol.
(1999) EphrinB ligands recruit GRIP family PDZ adaptor proteins into raft membrane microdomains
Neuron
(1999)Eph family receptors and their ligands distribute in opposing gradients in the developing mouse retina
Dev. Biol.
(1996)Expression and tyrosine phosphorylation of Eph receptors suggest multiple mechanisms in patterning of the visual system
Dev. Biol.
(1998)Modulation of EphA receptor function by coexpressed ephrin-A ligands on retinal ganglion cell axons
Neuron
(1999)- et al.
Development of the visual system of the chick. I. Cell differentiation and histogenesis
Brain Res. Brain Res. Rev.
(2000) - et al.
Development of the visual system of the chick. II. Mechanisms of axonal guidance
Brain Res. Brain Res. Rev.
(2001)