The Experts below are selected from a list of 879 Experts worldwide ranked by ideXlab platform
Adrian Pini - One of the best experts on this subject based on the ideXlab platform.
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On the topographic targeting of basal vomeronasal axons through Slit-mediated Chemorepulsion
Development (Cambridge England), 2003Co-Authors: Bernd Knöll, Sarah Guthrie, Adrian Pini, Vasi Sundaresan, Hannes Schmidt, William Andrews, Uwe DrescherAbstract:The vomeronasal projection conveys information provided by pheromones and detected by neurones in the vomeronasal organ (VNO) to the accessory olfactory bulb (AOB) and thence to other regions of the brain such as the amygdala. The VNO-AOB projection is topographically organised such that axons from apical and basal parts of the VNO terminate in the anterior and posterior AOB respectively. We provide evidence that the Slit family of axon guidance molecules and their Robo receptors contribute to the topographic targeting of basal vomeronasal axons. Robo receptor expression is confined largely to basal VNO axons, while Slits are differentially expressed in the AOB with a higher concentration in the anterior part, which basal axons do not invade. Immunohistochemistry using a Robo-specific antibody reveals a zone-specific targeting of VNO axons in the AOB well before cell bodies of these neurones in the VNO acquire their final zonal position. In vitro assays show that Slit1-Slit3 chemorepel VNO axons, suggesting that basal axons are guided to the posterior AOB due to chemorepulsive activity of Slits in the anterior AOB. These data in combination with recently obtained other data suggest a model for the topographic targeting in the vomeronasal projection where ephrin-As and neuropilins guide apical VNO axons, while Robo/Slit interactions are important components in the targeting of basal VNO axons.
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Slit proteins are not dominant chemorepellents for olfactory tract and spinal motor axons
Development (Cambridge England), 2001Co-Authors: Kalpana Patel, Julia A. B. Nash, Akira Itoh, Zhe Liu, Vasi Sundaresan, Adrian PiniAbstract:Members of the Slit family are large extracellular glycoproteins that may function as chemorepellents in axon guidance and neuronal cell migration. Their actions are mediated through members of the Robo family that act as their receptors. In vertebrates, Slit causes Chemorepulsion of embryonic olfactory tract, spinal motor, hippocampal and retinal ganglion cell axons. Since Slits are expressed in the septum and floor plate during the period when these tissues cause Chemorepulsion of olfactory tract and spinal motor axons respectively, it has been proposed that Slits function as guidance cues. We have tested this hypothesis in collagen gel co-cultures using soluble Robo/Fc chimeras, as competitive inhibitors, to disrupt Slit interactions. We find that the addition of soluble Robo/Fc has no effect on Chemorepulsion of olfactory tract and spinal motor axons when co-cultured with septum or floor plate respectively. Thus, we conclude that although Slits are expressed in the septum and floor plate, their proteins do not contribute to the major chemorepulsive activities emanating from these tissues which cause repulsion of olfactory tract and spinal motor axons.
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Surround repulsion of spinal sensory axons in higher vertebrate embryos.
Neuron, 1997Co-Authors: Roger J. Keynes, David Tannahill, Daniel A. Morgenstern, Alan R. Johnson, Geoffrey M.w. Cook, Adrian PiniAbstract:We have tested whether the orientation of axons sprouting from bipolar dorsal root ganglion neurons is influenced by diffusible cues from surrounding tissues. Surface ectoderm, dermomyotome, and notochord exert strong Chemorepulsion on axons growing in collagen gels, operating at separations beyond those found in vivo and active in cocultures of chick and mouse tissues. Basal and alar plates of the neural tube are devoid of activity, as is the posterior-half-sclerotome, which repels in a contact-dependent manner. When ganglia are sandwiched between dermomyotome and notochord placed at a distance, axon growth is channeled in a bipolar trajectory. These results show that gradients of diffusible repulsion molecules flanking axon pathways can generate linear patterns of axon growth. We suggest that such "surround repulsion" may function generally, in concert with contact-dependent guidance mechanisms, to guide axons in the developing nervous system.
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Chemorepulsion of developing motor axons by the floor plate
Neuron, 1995Co-Authors: Sarah Guthrie, Adrian PiniAbstract:In the developing nervous system, motor axons grow away from the ventral midline floor plate, suggesting that the latter might be a source of repulsive axonal guidance cues. In donor to host transplantation experiments, ectopic pieces of floor plate were positioned between chick hindbrain motor neurons and their exit points. Immunohistochemistry and retrograde axonal labeling techniques demonstrated that motor axons diverted from their normal pathways to avoid grafted floor plate, often traversing abnormally long circuitous trajectories to reach exit points. When ventral explants of rat hindbrain and spinal cord were cocultured at a distance from floor plate explants within collagen gel matrices, the outgrowth of motor axons was dramatically reduced from explant borders that faced the floor plate. Thus, the floor plate secretes diffusible repulsive cues in vitro that may exclude motor axons from the midline during development.
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Chemorepulsion of axons in the developing mammalian central nervous system
Science (New York N.Y.), 1993Co-Authors: Adrian PiniAbstract:During development of the nervous system, distinct populations of nerve cells extend specialized processes, axons and dendrites, over considerable distances to locate their targets. There is strong evidence for two general mechanisms by which these connections are made. The first involves attractive and repulsive interactions, both between cells and between them and their extracellular matrix. The second depends on the release of diffusible chemoattractants by target structures. Evidence is now provided for a mechanism of axon guidance in which diffusible chemorepulsive factors create exclusion zones for developing axons, causing them to turn away from inappropriate territory.
Elyanne M. Ratcliffe - One of the best experts on this subject based on the ideXlab platform.
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slit robo mediated Chemorepulsion of vagal sensory axons in the fetal gut
Developmental Dynamics, 2013Co-Authors: David Goldberg, Rajka Borojevic, Monique Anderson, Jason Chen, Michael D. Gershon, Elyanne M. RatcliffeAbstract:Background: The vagus nerve descends from the brain to the gut during fetal life to reach specific targets in the bowel wall. Vagal sensory axons have been shown to respond to the axon guidance molecule netrin and to its receptor, deleted in colorectal cancer (DCC). As there are regions of the gut wall into which vagal axons do and do not extend, it is likely that a combination of attractive and repellent cues are involved in how vagal axons reach specific targets. We tested the hypothesis that Slit/Robo Chemorepulsion can contribute to the restriction of vagal sensory axons to specific targets in the gut wall. Results: Transcripts encoding Robo1 and Robo2 were expressed in the nodose ganglia throughout development and mRNA encoding the Robo ligands Slit1, Slit2, and Slit3 were all found in the fetal and adult bowel. Slit2 protein was located in the outer gut mesenchyme in regions that partially overlap with the secretion of netrin-1. Neurites extending from explanted nodose ganglia were repelled by Slit2. Conclusions: These observations suggest that vagal sensory axons are responsive to Slit proteins and are thus repelled by Slits secreted in the gut wall and prevented from reaching inappropriate targets. Developmental Dynamics 242:9–15, 2013. © 2012 Wiley Periodicals, Inc.
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Slit/Robo‐mediated Chemorepulsion of vagal sensory axons in the fetal gut
Developmental dynamics : an official publication of the American Association of Anatomists, 2012Co-Authors: David Goldberg, Rajka Borojevic, Monique Anderson, Jason Chen, Michael D. Gershon, Elyanne M. RatcliffeAbstract:Background: The vagus nerve descends from the brain to the gut during fetal life to reach specific targets in the bowel wall. Vagal sensory axons have been shown to respond to the axon guidance molecule netrin and to its receptor, deleted in colorectal cancer (DCC). As there are regions of the gut wall into which vagal axons do and do not extend, it is likely that a combination of attractive and repellent cues are involved in how vagal axons reach specific targets. We tested the hypothesis that Slit/Robo Chemorepulsion can contribute to the restriction of vagal sensory axons to specific targets in the gut wall. Results: Transcripts encoding Robo1 and Robo2 were expressed in the nodose ganglia throughout development and mRNA encoding the Robo ligands Slit1, Slit2, and Slit3 were all found in the fetal and adult bowel. Slit2 protein was located in the outer gut mesenchyme in regions that partially overlap with the secretion of netrin-1. Neurites extending from explanted nodose ganglia were repelled by Slit2. Conclusions: These observations suggest that vagal sensory axons are responsive to Slit proteins and are thus repelled by Slits secreted in the gut wall and prevented from reaching inappropriate targets. Developmental Dynamics 242:9–15, 2013. © 2012 Wiley Periodicals, Inc.
Marc Tessier-lavigne - One of the best experts on this subject based on the ideXlab platform.
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UNC5C is required for spinal accessory motor neuron development.
Molecular and cellular neurosciences, 2007Co-Authors: Allison K. Dillon, Marc Tessier-lavigne, Lindsay Hinck, A.r. Jevince, Susan L. Ackerman, Zaven KaprielianAbstract:In both invertebrates and vertebrates, UNC5 receptors facilitate Chemorepulsion away from a Netrin source. Unlike most motor neurons in the embryonic vertebrate spinal cord, spinal accessory motor neuron (SACMN) cell bodies and their axons translocate along a dorsally directed trajectory away from the floor plate/ventral midline and toward the lateral exit point (LEP). We have recently shown that Netrin-1 and DCC are required for the migration of SACMN cell bodies, in vivo. These observations raised the possibility that vertebrate UNC5 proteins mediate the presumed repulsion of SACMN away from the Netrin-rich ventral midline. Here, we show that SACMN are likely to express UNC5A and UNC5C. Whereas SACMN development proceeds normally in UNC5A null mice, many SACMN cell bodies fail to migrate away from the ventral midline and inappropriately cluster in the ventrolateral spinal cord of mouse embryos lacking UNC5C. These results support an important role for UNC5C in SACMN development.
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Netrin 1 mediates spinal cord oligodendrocyte precursor dispersal.
Development (Cambridge England), 2003Co-Authors: Hui-hsin Tsai, Marc Tessier-lavigne, Robert H. MillerAbstract:In spinal cord, oligodendrocyte precursors that give rise to myelin-forming cells originate in a restricted domain of the ventral ventricular zone. During development, these cells migrate widely throughout the spinal cord. Netrin 1 is expressed at the ventral ventricular zone during oligodendrocyte precursors emigration, and, in vitro, netrin 1 acts as chemorepellent and antagonizes platelet-derived growth factor (PDGF) chemoattraction. Oligodendrocyte precursors express the netrin receptors DCC and UNC5 and function-blocking anti-DCC antibody inhibits Chemorepulsion of ventral spinal cord explants and netrin-secreting cells. In spinal cord slice preparations, addition of function-blocking anti-DCC antibody or netrin 1 dramatically inhibits oligodendrocyte precursor migration from the ventral ventricular zone. These data indicate the initial dispersal of oligodendrocyte precursors from their localized origin is guided by a chemorepellent response to netrin 1.
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Differential non-target-derived repulsive signals play a critical role in shaping initial axonal growth of dorsal root ganglion neurons.
Developmental biology, 2003Co-Authors: Tomoyuki Masuda, Hiroshi Tsuji, Masahiko Taniguchi, Takeshi Yagi, Marc Tessier-lavigne, Hajime Fujisawa, Nobuo Okado, Takashi ShigaAbstract:Abstract Initial trajectories of dorsal root ganglion (DRG) axons are shaped by chemorepulsive signals from surrounding tissues. Although we have previously shown that axonin-1/SC2 expression on DRG axons is required to mediate a notochord-derived chemorepulsive signal (T. Masuda et al., 2000 , Dev. Biol. 224, 112–121), other molecules involved in the non-target-derived repulsive signals are largely unknown. Using coculture assays composed of tissues derived from the chick embryo or mutant mice treated with function-blocking antibodies and phosphatidylinositol-specific phospholipase C, we report here that the chemorepellent semaphorin 3A (Sema3A) and its receptor neuropilin-1 are required for mediating the dermamyotome- and notochord-derived, but not the ventral spinal cord-derived, chemorepulsive signal for DRG axons. The dermamyotome-derived Chemorepulsion is exclusively dependent on Sema3A/neuropilin-1, whereas other molecules are also involved in the notochord-derived Chemorepulsion. Chemorepulsion from the ventral spinal cord does not depend on Sema3A/neuropilin-1 but requires axonin-1/SC2 to repel DRG axons. Thus, differential chemorepulsive signals help shape the initial trajectories of DRG axons and are critical for the proper wiring of the nervous system.
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Slit2-Mediated Chemorepulsion and Collapse of Developing Forebrain Axons
Neuron, 1999Co-Authors: Kim Tuyen Nguyen Ba-charvet, Corey S Goodman, Marc Tessier-lavigne, Katja Brose, Valérie Marillat, Thomas Kidd, Constantino Sotelo, Alain ChédotalAbstract:Diffusible chemorepellents play a major role in guiding developing axons toward their correct targets by preventing them from entering or steering them away from certain regions. Genetic studies in Drosophila revealed a novel repulsive guidance system that prevents inappropriate axons from crossing the CNS midline; this repulsive system is mediated by the Roundabout (Robo) receptor and its secreted ligand Slit. In rodents, Robo and Slit are expressed in the spinal cord and Slit can repel spinal motor axons in vitro. Here, we extend these findings into higher brain centers by showing that Robo1 and Robo2, as well as Slit1 and Slit2, are often expressed in complementary patterns in the developing forebrain. Furthermore, we show that human Slit2 can repel olfactory and hippocampal axons and collapse their growth cones.
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Semaphorins III and IV repel hippocampal axons via two distinct receptors
Development (Cambridge England), 1998Co-Authors: Alain Chédotal, Corey S Goodman, Marc Tessier-lavigne, Fernando De Castro, J. A. Del Rio, M.j. Ruiz, Víctor Borrell, Frédéric Ezan, Constantino SoteloAbstract:The semaphorins are the largest family of repulsive axon guidance molecules. Secreted semaphorins bind neuropilin receptors and repel sensory, sympathetic and motor axons. Here we show that CA1, CA3 and dentate gyrus axons from E15-E17 mouse embryo explants are selectively repelled by entorhinal cortex and neocortex. The secreted semaphorins Sema III and Sema IV and their receptors Neuropilin-1 and −2 are expressed in the hippocampal formation during appropriate stages. Sema III and Sema IV strongly repel CA1, CA3 and dentate gyrus axons; entorhinal axons are only repelled by Sema III. An antibody against Neuropilin-1 blocks the repulsive action of Sema III and the entorhinal cortex, but has no effect on Sema IV-induced repulsion. Thus, Chemorepulsion plays a role in axon guidance in the hippocampus, secreted semaphorins are likely to be responsible for this action, and the same axons can be repelled by two distinct semaphorins via two different receptors.
Sarah Guthrie - One of the best experts on this subject based on the ideXlab platform.
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Slit and Netrin-1 guide cranial motor axon pathfinding via Rho-kinase, myosin light chain kinase and myosin II.
Neural development, 2010Co-Authors: Ailish Murray, Arifa Naeem, Sarah H. Barnes, Uwe Drescher, Sarah GuthrieAbstract:Background In the developing hindbrain, cranial motor axon guidance depends on diffusible repellent factors produced by the floor plate. Our previous studies have suggested that candidate molecules for mediating this effect are Slits, Netrin-1 and Semaphorin3A (Sema3A). It is unknown to what extent these factors contribute to floor plate-derived Chemorepulsion of motor axons, and the downstream signalling pathways are largely unclear.
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On the topographic targeting of basal vomeronasal axons through Slit-mediated Chemorepulsion
Development (Cambridge England), 2003Co-Authors: Bernd Knöll, Sarah Guthrie, Adrian Pini, Vasi Sundaresan, Hannes Schmidt, William Andrews, Uwe DrescherAbstract:The vomeronasal projection conveys information provided by pheromones and detected by neurones in the vomeronasal organ (VNO) to the accessory olfactory bulb (AOB) and thence to other regions of the brain such as the amygdala. The VNO-AOB projection is topographically organised such that axons from apical and basal parts of the VNO terminate in the anterior and posterior AOB respectively. We provide evidence that the Slit family of axon guidance molecules and their Robo receptors contribute to the topographic targeting of basal vomeronasal axons. Robo receptor expression is confined largely to basal VNO axons, while Slits are differentially expressed in the AOB with a higher concentration in the anterior part, which basal axons do not invade. Immunohistochemistry using a Robo-specific antibody reveals a zone-specific targeting of VNO axons in the AOB well before cell bodies of these neurones in the VNO acquire their final zonal position. In vitro assays show that Slit1-Slit3 chemorepel VNO axons, suggesting that basal axons are guided to the posterior AOB due to chemorepulsive activity of Slits in the anterior AOB. These data in combination with recently obtained other data suggest a model for the topographic targeting in the vomeronasal projection where ephrin-As and neuropilins guide apical VNO axons, while Robo/Slit interactions are important components in the targeting of basal VNO axons.
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Chemorepulsion of developing motor axons by the floor plate
Neuron, 1995Co-Authors: Sarah Guthrie, Adrian PiniAbstract:In the developing nervous system, motor axons grow away from the ventral midline floor plate, suggesting that the latter might be a source of repulsive axonal guidance cues. In donor to host transplantation experiments, ectopic pieces of floor plate were positioned between chick hindbrain motor neurons and their exit points. Immunohistochemistry and retrograde axonal labeling techniques demonstrated that motor axons diverted from their normal pathways to avoid grafted floor plate, often traversing abnormally long circuitous trajectories to reach exit points. When ventral explants of rat hindbrain and spinal cord were cocultured at a distance from floor plate explants within collagen gel matrices, the outgrowth of motor axons was dramatically reduced from explant borders that faced the floor plate. Thus, the floor plate secretes diffusible repulsive cues in vitro that may exclude motor axons from the midline during development.
David Goldberg - One of the best experts on this subject based on the ideXlab platform.
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slit robo mediated Chemorepulsion of vagal sensory axons in the fetal gut
Developmental Dynamics, 2013Co-Authors: David Goldberg, Rajka Borojevic, Monique Anderson, Jason Chen, Michael D. Gershon, Elyanne M. RatcliffeAbstract:Background: The vagus nerve descends from the brain to the gut during fetal life to reach specific targets in the bowel wall. Vagal sensory axons have been shown to respond to the axon guidance molecule netrin and to its receptor, deleted in colorectal cancer (DCC). As there are regions of the gut wall into which vagal axons do and do not extend, it is likely that a combination of attractive and repellent cues are involved in how vagal axons reach specific targets. We tested the hypothesis that Slit/Robo Chemorepulsion can contribute to the restriction of vagal sensory axons to specific targets in the gut wall. Results: Transcripts encoding Robo1 and Robo2 were expressed in the nodose ganglia throughout development and mRNA encoding the Robo ligands Slit1, Slit2, and Slit3 were all found in the fetal and adult bowel. Slit2 protein was located in the outer gut mesenchyme in regions that partially overlap with the secretion of netrin-1. Neurites extending from explanted nodose ganglia were repelled by Slit2. Conclusions: These observations suggest that vagal sensory axons are responsive to Slit proteins and are thus repelled by Slits secreted in the gut wall and prevented from reaching inappropriate targets. Developmental Dynamics 242:9–15, 2013. © 2012 Wiley Periodicals, Inc.
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Slit/Robo‐mediated Chemorepulsion of vagal sensory axons in the fetal gut
Developmental dynamics : an official publication of the American Association of Anatomists, 2012Co-Authors: David Goldberg, Rajka Borojevic, Monique Anderson, Jason Chen, Michael D. Gershon, Elyanne M. RatcliffeAbstract:Background: The vagus nerve descends from the brain to the gut during fetal life to reach specific targets in the bowel wall. Vagal sensory axons have been shown to respond to the axon guidance molecule netrin and to its receptor, deleted in colorectal cancer (DCC). As there are regions of the gut wall into which vagal axons do and do not extend, it is likely that a combination of attractive and repellent cues are involved in how vagal axons reach specific targets. We tested the hypothesis that Slit/Robo Chemorepulsion can contribute to the restriction of vagal sensory axons to specific targets in the gut wall. Results: Transcripts encoding Robo1 and Robo2 were expressed in the nodose ganglia throughout development and mRNA encoding the Robo ligands Slit1, Slit2, and Slit3 were all found in the fetal and adult bowel. Slit2 protein was located in the outer gut mesenchyme in regions that partially overlap with the secretion of netrin-1. Neurites extending from explanted nodose ganglia were repelled by Slit2. Conclusions: These observations suggest that vagal sensory axons are responsive to Slit proteins and are thus repelled by Slits secreted in the gut wall and prevented from reaching inappropriate targets. Developmental Dynamics 242:9–15, 2013. © 2012 Wiley Periodicals, Inc.