title: Regulation of axon guidance by slit and netrin signaling in the Drosophila ventral nerve cord.
abstract: Netrin and Slit signaling systems play opposing roles during the positioning of longitudinal tracts along the midline in the ventral nerve cord of Drosophila embryo. It has been hypothesized that a gradient of Slit from the midline interacts with three different Robo receptors to specify the axon tract positioning. However, no such gradient has been detected. Moreover, overexpression of Slit at the midline has no effect on the positioning of these lateral tracts. In this article, we show that Slit is present outside of the midline along the longitudinal and commissural tracts. Sli from the midline, in a Robo-independent manner, is initially taken up by the commissural axon tracts when they cross the midline and is transported along the commissural tracts into the longitudinal connectives. These results are not consistent with a Sli gradient model. We also find that sli mRNA is maternally deposited and embryos that are genetically null for sli can have weaker guidance defects. Moreover, in robo or robo3 mutants, embryos with normal axon tracts are found and such robo embryos reach pupal stages and die, while robo3 mutant embryos develop into normal individuals and produce eggs. Interestingly, embryos from robo3 homozygous individuals fail to develop but have axon tracts ranging from normal to various defects: robo3 phenotype, robo phenotype, and slit-like phenotype, suggesting a more complex functional role for these genes than what has been proposed. Finally, our previous results indicated that netrin phenotype is epistatic to sli or robo phenotypes. However, it seems likely that this previously reported epistatic relationship might be due to the partial penetrance of the sli, robo, robo3 (or robo2) phenotypes. Our results argue that double mutant epistasis is most definitive only if the penetrance of the phenotypes of the mutants involved is complete.
authors.affiliation: Department of Neuroscience and Cell Biology, School of Medicine, University of Texas Medical Branch, Galveston, TX 77555, USA. kmbhat@UTMB.EDU
authors.forename: Krishna Moorthi
authors.initials: KM
authors.lastname: Bhat
authors.forename: Ivana
authors.initials: I
authors.lastname: Gaziova
authors.forename: Smitha
authors.initials: S
authors.lastname: Krishnan
mesh_terms: D000818:Animals; D001370:Axonal Transport; D001369:Axons / Q000378:metabolism / Q000648:ultrastructure; D001483:Base Sequence; D051792:Basic Helix-Loop-Helix Proteins / Q000235:genetics / Q000378:metabolism*; D017931:DNA Primers / Q000235:genetics; D004330:Drosophila / Q000196:embryology* / Q000235:genetics / Q000378:metabolism*; D029721:Drosophila Proteins / Q000235:genetics / Q000378:metabolism*; D004843:Epistasis, Genetic; D005260:Female; D017344:Genes, Insect; D008297:Male; D009154:Mutation; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism*; D009420:Nervous System / Q000196:embryology* / Q000378:metabolism*; D000075386:Netrin Receptors; D010641:Phenotype; D011956:Receptors, Cell Surface / Q000235:genetics / Q000378:metabolism; D011971:Receptors, Immunologic / Q000235:genetics / Q000378:metabolism; D012097:Repressor Proteins / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction; D000097905:Roundabout Proteins
chemical_list: D051792:Basic Helix-Loop-Helix Proteins; D017931:DNA Primers; D029721:Drosophila Proteins; D009419:Nerve Tissue Proteins; D000075386:Netrin Receptors; D011956:Receptors, Cell Surface; D011971:Receptors, Immunologic; D012097:Repressor Proteins; D000097905:Roundabout Proteins; C417033:net protein, Drosophila; C066819:sli protein, Drosophila