The Experts below are selected from a list of 60 Experts worldwide ranked by ideXlab platform
Stefan Thor - One of the best experts on this subject based on the ideXlab platform.
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segment specific prevention of Pioneer Neuron apoptosis by cell autonomous postmitotic hox gene activity
Development, 2004Co-Authors: Irene Miguelaliaga, Stefan ThorAbstract:In vertebrates, Neurons often undergo apoptosis after differentiating and extending their axons. By contrast, in the developing nervous system of invertebrate embryos apoptosis typically occurs soon after cells are generated. Here, we show that the Drosophila dMP2 and MP1 Pioneer Neurons undergo segment-specific apoptosis at late embryonic stages, long after they have extended their axons and have performed their Pioneering role in guiding follower axons. This segmental specificity is achieved by differential expression of the Hox gene Abdominal B, which in posterior segments prevents Pioneer Neuron death postmitotically and cell-autonomously by repressing the RHG-motif cell death activators reaper and grim. Our results identify the first clear case of a cell-autonomous and anti-apoptotic role for a Hox gene in vivo. In addition, they provide a novel mechanism linking Hox positional information to differences in Neuronal architecture along the anteroposterior axis by the selective elimination of mature Neurons.
Irene Miguelaliaga - One of the best experts on this subject based on the ideXlab platform.
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segment specific prevention of Pioneer Neuron apoptosis by cell autonomous postmitotic hox gene activity
Development, 2004Co-Authors: Irene Miguelaliaga, Stefan ThorAbstract:In vertebrates, Neurons often undergo apoptosis after differentiating and extending their axons. By contrast, in the developing nervous system of invertebrate embryos apoptosis typically occurs soon after cells are generated. Here, we show that the Drosophila dMP2 and MP1 Pioneer Neurons undergo segment-specific apoptosis at late embryonic stages, long after they have extended their axons and have performed their Pioneering role in guiding follower axons. This segmental specificity is achieved by differential expression of the Hox gene Abdominal B, which in posterior segments prevents Pioneer Neuron death postmitotically and cell-autonomously by repressing the RHG-motif cell death activators reaper and grim. Our results identify the first clear case of a cell-autonomous and anti-apoptotic role for a Hox gene in vivo. In addition, they provide a novel mechanism linking Hox positional information to differences in Neuronal architecture along the anteroposterior axis by the selective elimination of mature Neurons.
Yoshiki Hotta - One of the best experts on this subject based on the ideXlab platform.
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The Drosophila Netrin receptor Frazzled guides axons by controlling Netrin distribution
Nature, 2000Co-Authors: Masaki Hiramoto, Yasushi Hiromi, Edward Giniger, Yoshiki HottaAbstract:Netrin is a secreted protein that can act as a chemotropic axon guidance cue1,2. Two classes of Netrin receptor, DCC3,4,5 and UNC-5 (refs 6,7,8,9), are required for axon guidance3,4,6,7,8,9,10,11 and are thought to mediate Netrin signals in growth cones through their cytoplasmic domains12,13. However, in the guidance of Drosophila photoreceptor axons, the DCC orthologue Frazzled3 is required not in the photoreceptor Neurons but instead in their targets, indicating that Frazzled also has a non-cell-autonomous function14. Here we show that Frazzled can capture Netrin and ‘present’ it for recognition by other receptors. Moreover, Frazzled itself is actively localized within the axon through its cytoplasmic domain, and thereby rearranges Netrin protein into a spatial pattern completely different from the pattern of Netrin gene expression. Frazzled-dependent guidance of one Pioneer Neuron in the central nervous system can be accounted for solely on the basis of this ability of Frazzled to control Netrin distribution, and not by Frazzled signalling. We propose a model of patterning mechanism in which a receptor rearranges secreted ligand molecules, thereby creating positional information for other receptors.
Masaki Hiramoto - One of the best experts on this subject based on the ideXlab platform.
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The Drosophila Netrin receptor Frazzled guides axons by controlling Netrin distribution
Nature, 2000Co-Authors: Masaki Hiramoto, Yasushi Hiromi, Edward Giniger, Yoshiki HottaAbstract:Netrin is a secreted protein that can act as a chemotropic axon guidance cue1,2. Two classes of Netrin receptor, DCC3,4,5 and UNC-5 (refs 6,7,8,9), are required for axon guidance3,4,6,7,8,9,10,11 and are thought to mediate Netrin signals in growth cones through their cytoplasmic domains12,13. However, in the guidance of Drosophila photoreceptor axons, the DCC orthologue Frazzled3 is required not in the photoreceptor Neurons but instead in their targets, indicating that Frazzled also has a non-cell-autonomous function14. Here we show that Frazzled can capture Netrin and ‘present’ it for recognition by other receptors. Moreover, Frazzled itself is actively localized within the axon through its cytoplasmic domain, and thereby rearranges Netrin protein into a spatial pattern completely different from the pattern of Netrin gene expression. Frazzled-dependent guidance of one Pioneer Neuron in the central nervous system can be accounted for solely on the basis of this ability of Frazzled to control Netrin distribution, and not by Frazzled signalling. We propose a model of patterning mechanism in which a receptor rearranges secreted ligand molecules, thereby creating positional information for other receptors.
Claire Y. Bénard - One of the best experts on this subject based on the ideXlab platform.
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HS chain elongation is required for unc-6/Netrin-signaling in axon guidance.
2017Co-Authors: Cassandra R. Blanchette, Andrea Thackeray, Paola N. Perrat, Siegfried Hekimi, Claire Y. BénardAbstract:A. We visualized the morphology of the AVM and PVM axons using the transgene Pmec-4::gfp. Scale bar, 50 μm. B. During the first larval stage of wild-type C. elegans, the Pioneer Neuron AVM extends ventrally along the body wall until it reaches the ventral nerve cord. Its migration results from the combined attractive response to UNC-6/Netrin (secreted at the ventral midline) via the UNC-40/DCC receptor, and the repulsive response to SLT-1/Slit (secreted by the dorsal muscles) via its SAX-3/Robo receptor. Loss of rib-1 or rib-2 combined with defective unc-6/Netrin function using the hypomorphic allele of unc-6(e78), results in more severely affected AVM guidance. Hypomorphic allele unc-6(e78) was used here because the double mutants of rib-1(qm32) or rib-2(qm46) with the null allele unc-6(ev400) died as embryos. Combining mutations rib-1(qm32)m-/-z-/- or rib-2(qm46)m-/-z-/- with conditions where slt-1/Slit signaling is disrupted, either with the presumptive null allele slt-1(eh15) or in animals misexpressing slt-1 in all body wall muscles (using a Pmyo-3::slt-1 transgene), leads to more severe AVM defects that in either single condition alone. That the AVM axon guidance defects of mutants in both key guidance pathways, slt-1 and unc-6, are worsened by loss of rib-1 or rib-2 is consistent with the notion that HS chains function in both of these pathways, and/or function in yet another unidentified pathway. Scale bar, 5 μm. C. unc-6/Netrin signaling via the unc-5/UNC5 receptor requires functional HS chains. The Pioneer axon of PVM normally migrates ventrally; however, upon misexpression of unc-5/UNC5 in PVM using the transgene Pmec-7::unc-5, the axon of PVM projects dorsally in an unc-6/Netrin- and unc-40/DCC-dependent manner. Loss of function of the genes rib-1 or rib-2 partially suppresses this forced dorsal migration, indicating that unc-6/Netrin signaling depends on functional HS chains. Null allele unc-6(ev400) was used in this experiment. Scale bar, 5 μm. D. HS modifying enzymes function in the unc-6/Netrin- and slt-1/Slit mediated-guidance of the AVM axon. Complete loss of HS modifying enzymes, including the epimerase hse-5 and the sulfotransferases hst-2 and hst-6, enhance the AVM guidance defects of unc-6/Netrin and slt-1/Slit mutants null mutants [unc-6(ev400) and slt-1(eh15)], consistent with the notion that proper HS chain modifications are important in guiding AVM through both the unc-6/Netrin and slt-1/Slit pathways, and/or possibly for another unidentified pathway. Error bars are standard error of the proportion. Asterisks denote significant difference: *** P ≤ 0.001, ** P ≤ 0.01, * P ≤ 0.05 (z-tests, P values were corrected by multiplying by the number of comparisons). ns, not significant. See S6, S7, and S8 Tables.
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lon-2/glypican functions in the attractive unc-6/netrin guidance pathway.
2015Co-Authors: Cassandra R. Blanchette, Andrea Thackeray, Paola N. Perrat, Claire Y. BénardAbstract:(A) During the first larval stage of C. elegans, the Pioneer Neuron AVM extends ventrally along the body wall until it reaches the ventral nerve cord. Its migration results from the combined attractive response to UNC-6/netrin (secreted at the ventral midline) via the UNC-40/DCC receptor and the repulsive response to SLT-1/Slit (secreted by the dorsal muscles) via its SAX-3/Robo receptor. We visualized the morphology of the AVM axon using the transgene Pmec-4::gfp. (B) The heparan sulfate proteoglycans lon-2/glypican and sdn-1/syndecan cooperate to guide the axon of AVM, as their simultaneous loss enhances guidance defects. The role of lon-2/glypican in axon guidance is specific, as the loss of lon-2/glypican, but not the loss of the other C. elegans glypican, gpn-1, enhances the defects of sdn-1/syndecan mutants. (C) Complete loss of lon-2/glypican enhances the axon guidance defects resulting from disrupted slt-1/Slit signaling in mutants for slt-1/Slit or its receptor sax-3/Robo, as well as in animals misexpressing slt-1 in all body wall muscles (using a Pmyo-3::slt-1 transgene). Data for wild type and lon-2 are the same as in (B). (D) Complete loss of lon-2/glypican does not enhance the AVM guidance defects of unc-6/netrin mutants or of mutants for its receptor unc-40/DCC, suggesting that lon-2/glypican functions in the same genetic pathway as unc-6/netrin. Data for wild type and lon-2 are the same as in (B). (E) Loss of sdn-1/syndecan function does not enhance the defects of slt-1/Slit or sax-3/Robo mutants but enhances the defects of unc-40/DCC mutants. Data for wild type, sdn-1, slt-1, sax-3, and unc-40 are the same as in (B–D). Error bars are standard error of the proportion. Asterisks denote significant difference\: *** p ≤ 0.001,** p ≤ 0.01, and * p ≤ 0.05 (z-tests, p-values were corrected by multiplying by the number of comparisons). ns, not significant.