Assembling a nervous system requires exquisite specificity in the construction ofneuronal connectivity. One method by which such specificity is implemented isthe presence of chemical cues within the tissues, differentiating one region fromanother, and the presence of receptors for those cues on the surface of neuronsand their axons that are navigating within this cellular environment.
Connections from one part of the nervous system to another often take the formof a topographic mapping. One widely studied model system that involves sucha mapping is the vertebrate retinotectal projection-the set of connectionsbetween the eye and the optic tectum of the midbrain, which is the primaryvisual center in non-mammals and is homologous to the superior colliculus inmammals. In this projection the two-dimensional surface of the retina is mappedsmoothly onto the two-dimensional surface of the tectum, such that light fromneighboring points in visual space excites neighboring cells in the brain. Thismapping is implemented at least in part via differential chemical cues indifferent regions of the tectum.
The Eph family of receptor tyrosine kinases and their cell-surface ligands, theephrins, have been implicated in a wide variety of processes, generally involvingcellular movement in response to extracellular cues. In particular, they possessexpression patterns-i.e., complementary gradients of receptor in retina andligand in tectum- and in vitro and in vivo activities and phenotypes-i.e.,repulsive guidance of axons and defective mapping in mutants,respectively-consistent with the long-sought retinotectal chemical mappingcues.
The tadpole of Xenopus laevis, the South African clawed frog, is advantageousfor in vivo retinotectal studies because of its transparency and manipulability.However, neither the expression patterns nor the retinotectal roles of theseproteins have been well characterized in this system. We report herecomprehensive descriptions in swimming stage tadpoles of the messenger RNAexpression patterns of eleven known Xenopus Eph and ephrin genes, includingxephrin-A3, which is novel, and xEphB2, whose expression pattern has notpreviously been published in detail. We also report the results of in vivo proteininjection perturbation studies on Xenopus retinotectal topography, which werenegative, and of in vitro axonal guidance assays, which suggest a previouslyunrecognized attractive activity of ephrins at low concentrations on retinalganglion cell axons. This raises the possibility that these axons find their correcttargets in part by seeking out a preferred concentration of ligands appropriate totheir individual receptor expression levels, rather than by being repelled togreater or lesser degrees by the ephrins but attracted by some as-yet-unknowncue(s).
