Abstract
Receptors of the Eph family of tyrosine kinases and their Ephrin ligands are involved in developmental processes as diverse as angiogenesis, axon guidance and cell migration. However, our understanding of the Eph signaling pathway is incomplete, and could benefit from an analysis by genetic methods. To this end, we performed a genetic modifier screen for mutations that affect Eph signaling in Drosophila melanogaster. Several dozen loci were identified on the basis of their suppression or enhancement of an eye defect induced by the ectopic expression of Ephrin during development; many of these mutant loci were found to disrupt visual system development. One modifier locus, reph (regulator of eph expression), was characterized in molecular detail and found to encode a putative nuclear protein that interacts genetically with Eph signaling pathway mutations. Reph is an autonomous regulator of Eph receptor expression, required for the graded expression of Eph protein and the establishment of an optic lobe axonal topographic map. These results reveal a novel component of the regulatory pathway controlling expression of eph and identify reph as a novel factor in the developing visual system.
Highlights
Bi-directional signaling through receptor tyrosine kinases of the Eph family and their Ephrin ligands contributes to diverse processes during and after development including the establishment of topographic axon projections in the visual system [1,2], cell migration [3,4], vascular development [5] and long-term potentiation [6,7,8]
While RNAi interference approaches have suggested a role for Eph/Ephrin signaling in neuronal development, notably within the embryonic CNS [21,36], analyses of Eph null mutants did not detect embryonic CNS defects but rather a specific role for Eph/Ephrin signaling in the developing mushroom body [22]
The disparity between these results suggests a complex role for Eph/Ephrin signaling during Drosophila development that would benefit from additional characterization, analyses of Ephrin expression patterns within the larval brain
Summary
Bi-directional signaling through receptor tyrosine kinases of the Eph family and their Ephrin ligands contributes to diverse processes during and after development including the establishment of topographic axon projections in the visual system [1,2], cell migration [3,4], vascular development [5] and long-term potentiation [6,7,8]. Crucial to deciphering the mechanisms by which this signaling pathway mediates such diverse and complex processes is a complete catalog of its pathway components. Substantial progress towards this end has been made by biochemical approaches [9]. A complementary approach, utilizing genetic analysis, offers the possibility of additional insights into Eph signal transduction. We have undertaken this approach in D. melanogaster
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