Integrins regulate responsiveness to slit repellent signals.
Integrins are concentrated within growth cones, but their contribution to axon extension and pathfinding is unclear. Genetic lesion of individual integrins does not stop growth cone extension or motility, but does increase axon defasciculation and axon tract displacement. In this study, we document a dosage-dependent phenotypic interaction between genes for the integrins, their ligands, and the midline growth cone repellent, Slit, but not for the midline attractant, Netrin. Longitudinal tract axons in Drosophila embryos doubly heterozygous for slit and an integrin gene, encoding alphaPS1, alphaPS2, alphaPS3, or betaPS1, take ectopic trajectories across the midline of the CNS. Drosophila doubly heterozygous for slit and the genes encoding the integrin ligands Laminin A and Tiggrin reveal similar errors in midline axon guidance. We propose that the strength of adhesive signaling from integrins influences the threshold of response by growth cones to repellent axon guidance cues.
Stevens
Adrienne
A
Department of Biology, McMaster University, Hamilton, Ontario, L8S 4K1, Canada.
Jacobs
J Roger
JR
D000818:Animals; D001369:Axons / Q000378:metabolism*; D004330:Drosophila; D029721:Drosophila Proteins; D004625:Embryo, Nonmammalian / Q000166:cytology / Q000294:innervation / Q000378:metabolism; D016326:Extracellular Matrix Proteins / Q000235:genetics / Q000378:metabolism; D018628:Gene Dosage; D015870:Gene Expression; D020439:Growth Cones / Q000378:metabolism; D006579:Heterozygote; D007150:Immunohistochemistry; D016023:Integrins / Q000235:genetics / Q000378:metabolism*; D007797:Laminin / Q000235:genetics / Q000378:metabolism; D008024:Ligands; D009154:Mutation; D009414:Nerve Growth Factors / Q000235:genetics / Q000378:metabolism; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism*; D000075388:Netrin-1; D000075385:Netrins; D019683:Penetrance; D010641:Phenotype; D015398:Signal Transduction / Q000502:physiology*; D025521:Tumor Suppressor Proteins
D029721:Drosophila Proteins; D016326:Extracellular Matrix Proteins; D016023:Integrins; D007797:Laminin; D008024:Ligands; D009414:Nerve Growth Factors; D009419:Nerve Tissue Proteins; D000075385:Netrins; C089678:Tig protein, Drosophila; D025521:Tumor Suppressor Proteins; C066819:sli protein, Drosophila; C084098:laminin A; D000075388:Netrin-1; C088894:netrin-2