The Experts below are selected from a list of 7776 Experts worldwide ranked by ideXlab platform
Jennifer Rodger - One of the best experts on this subject based on the ideXlab platform.
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Ephrin A2 affects wound healing and scarring in a murine model of excisional injury
Burns, 2019Co-Authors: Dulharie T Wijeratne, Jennifer Rodger, Andrew Stevenson, Hilary Wallace, Cecilia M Prele, Fiona M Wood, Mark W FearAbstract:Ephrin ligand/Eph receptor signaling is important in both tissue development and homeostasis. There is increasing evidence that Ephrin/Eph signaling is important in the skin, involved in hair follicle cycling, epidermal differentiation, cutaneous innervation and skin cancer. However, there is currently limited information on the role of Ephrin/Eph signaling in cutaneous wound healing. Here we report the effects of the Ephrin-A2 and A5 ligands on wound healing. Using Ephrin-A2-/-, Ephrin-A5-/- and Ephrin-A2A5-/- transgenic mice, in vitro wound healing assays were conducted using isolated keratinocytes and fibroblasts. Ephrin-A2-/-, Ephrin-A2A5-/- and wild type mice with excisional wounds were used to analyze the impact of these ligands on wound closure, scar outcome, collagen orientation and re-innervation in vivo. The absence of the Ephrin-A2 and A5 ligands did not have any effect on dermal fibroblast proliferation or on fibroblast or keratinocyte migration. The loss of Ephrin-A2 and A5 ligands did not impact on the rate of wound closure or re-innervation after injury. However, changes in the gross morphology of the healed scar and in collagen histology of the scar dermis were observed in transgenic mice. Therefore Ephrin-A2 and A5 ligands may play an important role in final scar appearance associated with collagen deposition and structure.
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Ephrin-A2 regulates excitatory neuron differentiation and interneuron migration in the developing neocortex.
Scientific reports, 2017Co-Authors: Jihane Homman-ludiye, Jennifer Rodger, William C. Kwan, Mitchell J. De Souza, James A. BourneAbstract:The development of the neocortex requires co-ordination between proliferation and differentiation, as well as the precise orchestration of neuronal migration. Eph/Ephrin signaling is crucial in guiding neurons and their projections during embryonic development. In adult Ephrin-A2 knockout mice we consistently observed focal patches of disorganized neocortical laminar architecture, ranging in severity from reduced neuronal density to a complete lack of neurons. Loss of Ephrin-A2 in the pre-optic area of the diencephalon reduced the migration of neocortex-bound interneurons from this region. Furthermore, Ephrin-A2 participates in the creation of excitatory neurons by inhibiting apical progenitor proliferation in the ventricular zone, with the disruption of Ephrin-A2 signaling in these cells recapitulating the abnormal neocortex observed in the knockout. The disturbance to the architecture of the neocortex observed following deletion of Ephrin-A2 signaling shares many similarities with defects found in the neocortex of children diagnosed with autism spectrum disorder.
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The role of Ephrin-A2 and Ephrin-A5 in sensorimotor control and gating.
Behavioural Brain Research, 2014Co-Authors: Nathanael J. Yates, Mathew T. Martin-iverson, Jennifer RodgerAbstract:Many factors influence neurodevelopment. However, their contribution to adult neural function is often unclear. This is often due to complex expression profiles, cell signalling, neuroanatomy, and a lack of effective tests to assess the function of neural circuits in vivo. Ephrin-A2 and Ephrin-A5 are cell surface proteins implicated in multiple aspects of neurodevelopment. While the role of Ephrin-As in visual, auditory and learning behaviours has been explored, little is known about their role in dopaminergic and neuromotor pathways, despite expression in associated brain regions. Here we probe the function of Ephrin-A2 and Ephrin-A5 in the development of the dopaminergic and neuromotor pathways using counts of tyrosine hydroxylase (TH) positive cells in the substantia nigra pars compacta (SNpc) and the ventral tegmental area (VIA), the acoustic startle reflex (ASR), and a measure of sensorimotor gating, prepulse inhibition (PPI). Analysis of the ASR and PPI in Ephrin-A2 and/or Ephrin-A5 knock-out mice revealed that both genes play distinct roles in mediating ASR circuits, but are unlikely to play a role in PPI. Knock-out of either gene resulted in robust changes in startle response magnitude and measures of startle onset and peak latencies. However, Ephrin-A2 and Ephrin-A5 regulate aspects of the ASR differently: Ephrin-A2 KO mice have increased startle amplitude, increased sensitivity and reduced latency to startle, whilst Ephrin-A5 KO mice show opposite effects. Neither of the gene knock outs affected PPI, despite Ephrin-A5 KO mice showing changes in dopamine cell numbers in nuclei thought to regulate PPI. We propose that majority of the changes observed Ephrin-A2 and Ephrin-A5 KO mice appear to be mediated by the effects on motor neurons and their muscle targets, rather than changes in auditory sensitivity. (C) 2014 Elsevier B.V. All rights reserved.
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The role of Ephrin-A2 and Ephrin-A5 in sensorimotor control and gating
Behavioural brain research, 2014Co-Authors: Nathanael J. Yates, Mathew T. Martin-iverson, Jennifer RodgerAbstract:Many factors influence neurodevelopment. However, their contribution to adult neural function is often unclear. This is often due to complex expression profiles, cell signalling, neuroanatomy, and a lack of effective tests to assess the function of neural circuits in vivo. Ephrin-A2 and Ephrin-A5 are cell surface proteins implicated in multiple aspects of neurodevelopment. While the role of Ephrin-As in visual, auditory and learning behaviours has been explored, little is known about their role in dopaminergic and neuromotor pathways, despite expression in associated brain regions. Here we probe the function of Ephrin-A2 and Ephrin-A5 in the development of the dopaminergic and neuromotor pathways using counts of tyrosine hydroxylase (TH) positive cells in the substantia nigra pars compacta (SNpc) and the ventral tegmental area (VTA), the acoustic startle reflex (ASR), and a measure of sensorimotor gating, prepulse inhibition (PPI). Analysis of the ASR and PPI in Ephrin-A2 and/or Ephrin-A5 knock-out mice revealed that both genes play distinct roles in mediating ASR circuits, but are unlikely to play a role in PPI. Knock-out of either gene resulted in robust changes in startle response magnitude and measures of startle onset and peak latencies. However, Ephrin-A2 and Ephrin-A5 regulate aspects of the ASR differently: Ephrin-A2 KO mice have increased startle amplitude, increased sensitivity and reduced latency to startle, whilst Ephrin-A5 KO mice show opposite effects. Neither of the gene knock outs affected PPI, despite Ephrin-A5 KO mice showing changes in dopamine cell numbers in nuclei thought to regulate PPI. We propose that majority of the changes observed Ephrin-A2 and Ephrin-A5 KO mice appear to be mediated by the effects on motor neurons and their muscle targets, rather than changes in auditory sensitivity.
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auditory brainstem responses of Ephrin A2 Ephrin a5 and Ephrin A2a5 mice
Audiology and Neuro-otology, 2014Co-Authors: Nathanael J. Yates, Donald Robertson, Mathew T Martiniverson, Jennifer RodgerAbstract:Eph receptors and Ephrin ligands are large families of cell surface proteins which have established roles in axonal growth and guidance. These are well characterized in the visual and somatosensory sy
David A Feldheim - One of the best experts on this subject based on the ideXlab platform.
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roles of Ephrin as and structured activity in the development of functional maps in the superior colliculus
The Journal of Neuroscience, 2008Co-Authors: Jianhua Cang, Michael P Stryker, Lupeng Wang, David A FeldheimAbstract:The orderly projections from retina to superior colliculus (SC) preserve a continuous retinotopic representation of the visual world. The development of retinocollicular maps depend on a combination of molecular guidance cues and patterned neural activity. Here, we characterize the functional retinocollicular maps in mice lacking the guidance molecules Ephrin-A2, -A3, and -A5 and in mice deficient in both Ephrin-As and structured spontaneous retinal activity, using a method of Fourier imaging of intrinsic signals. We find that the SC of Ephrin-A2/A3/A5 triple knock-out mice contains functional maps that are disrupted selectively along the nasotemporal (azimuth) axis of the visual space. These maps are discontinuous, with patches of SC responding to topographically incorrect locations. The patches disappear in mice that are deficient in both Ephrin-As and structured activity, resulting in a near-absence of azimuth map in the SC. These results indicate that Ephrin-As guide the formation of functional topography in the SC, and patterned retinal activity clusters cells based on their correlated firing patterns. Comparison of the SC and visual cortical mapping defects in these mice suggests that although Ephrin-As are required for mapping in both SC and visual cortex, Ephrin-A-independent mapping mechanisms are more important in visual cortex than in the SC.
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Ephrins as negative regulators of adult neurogenesis in diverse regions of the central nervous system
Proceedings of the National Academy of Sciences of the United States of America, 2008Co-Authors: Jianwei Jiao, David A Feldheim, Dong Feng ChenAbstract:In the central nervous system (CNS) of adult mammals, neurogenesis occurs in only two restricted areas, the subgranular zone (SGZ) of the hippocampus and the subventricular zone (SVZ). Isolation of multipotent progenitor cells from other CNS regions suggests that their neurogenic potential is dictated by local environmental cues. Here, we report that astrocytes in areas outside of the SGZ and SVZ of adult mice express high levels of Ephrin-A2 and -A3, which present an inhibitory niche, negatively regulating neural progenitor cell growth. Adult mice lacking both Ephrin-A2 and -A3 display active ongoing neurogenesis throughout the CNS. These findings suggest that neural cell replacement therapies for neurodegeneration or injury in the adult CNS may be achieved by manipulating Ephrin signaling pathways.
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Partial nucleotide sequences and expression patterns of frog (Rana pipiens) Ephrin-A2 and Ephrin-A5 mRNA.
Developmental Brain Research, 2005Co-Authors: Yoshiki Yagita, David A Feldheim, Isaac Barjis, Michael Hecht, Helene Bach, Frank ScaliaAbstract:We have generated 362 bp and 547 bp partial sequences for Rana pipiens Ephrin-A2 and Ephrin-A5 mRNA, respectively. Translation homologies for the comparable segments of cDNA of chicken, mouse and human are 90.8, 86.9 and 84.4% for the Ephrin-A2 sequence and 85.7, 85.0 and 85.0% for the Ephrin-A5 sequence. Digoxigenin-labeled riboprobes were prepared and applied by means of in situ hybridization to whole-mounts of the brains of mature adults and expression patterns in tadpoles were also explored. The RNA probes revealed similar posterior (high) to anterior (low) expression gradients in the adult tectum, demonstrating that both Ephrin-As are expressed in the adult Ranid frog tectum. Only the Ephrin-A2 probe was tested on tadpole brain, yielding an appropriately graded expression pattern similar to the adult.
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Ephrin as and neural activity are required for eye specific patterning during retinogeniculate mapping
Nature Neuroscience, 2005Co-Authors: Cory Pfeiffenberger, Jena Yamada, John G Flanagan, Georgia Woods, Tyler Cutforth, Rene C Renteria, David R Copenhagen, David A FeldheimAbstract:In mammals, retinal ganglion cell (RGC) projections initially intermingle and then segregate into a stereotyped pattern of eye-specific layers in the dorsal lateral geniculate nucleus (dLGN). Here we found that in mice deficient for Ephrin-A2, Ephrin-A3 and Ephrin-A5, eye-specific inputs segregated but the shape and location of eye-specific layers were profoundly disrupted. In contrast, mice that lacked correlated retinal activity did not segregate eye-specific inputs. Inhibition of correlated neural activity in Ephrin mutants led to overlapping retinal projections that were located in inappropriate regions of the dLGN. Thus, Ephrin-As and neural activity act together to control patterning of eye-specific retinogeniculate layers.
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Ephrin A2 and a5 influence patterning of normal and novel retinal projections to the thalamus conserved mapping mechanisms in visual and auditory thalamic targets
The Journal of Comparative Neurology, 2005Co-Authors: Charlene Ellsworth, David A Feldheim, John G Flanagan, Alvin W Lyckman, Mriganka SurAbstract:Sensory axons are targeted to modality-specific nuclei in the thalamus. Retinal ganglion cell axons project retinotopically to their principal thalamic target, the dorsal lateral geniculate nucleus (LGd), in a pattern likely dictated by the expression of molecular gradients in the LGd. Deafferenting the auditory thalamus induces retinal axons to innervate the medial geniculate nucleus (MGN). These retino-MGN projections also show retinotopic organization. Here we show that Ephrin-A2 and -A5, which are expressed in similar gradients in the MGN and LGd, can be used to pattern novel retinal projections in the MGN. As in the LGd, retinal axons from each eye terminate in discrete eye-specific zones in the MGN of rewired wild-type and Ephrin-A2/A5 knockout mice. However, ipsilateral eye axons, which arise from retinal regions of high EphA5 receptor expression and represent central visual field, terminate in markedly different ways in the two mice. In rewired wild-type mice, ipsilateral axons specifically avoid areas of high Ephrin expression in the MGN. In rewired Ephrin knockout mice, ipsilateral projections shift in location and spread more broadly, leading to an expanded representation of the ipsilateral eye in the MGN. Similarly, ipsilateral projections to the LGd in Ephrin knockout mice are shifted and are more widespread than in the LGd of wild-type mice. In the MGN, as in the LGd, terminations from the two eyes show little overlap even in the knockout mice, suggesting that local interocular segregation occurs regardless of other patterning determinants. Our data demonstrate that graded topographic labels, such as the Ephrins, can serve to shape multiple related aspects of afferent patterning, including topographic mapping and the extent and spread of eye-specific projections. Furthermore, when mapping labels and other cues are expressed in multiple target zones, novel projections are patterned according to rules that operate in their canonical targets. J. Comp. Neurol. 488:140–151, 2005. © 2005 Wiley-Liss, Inc.
John G Flanagan - One of the best experts on this subject based on the ideXlab platform.
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Ephrin as and neural activity are required for eye specific patterning during retinogeniculate mapping
Nature Neuroscience, 2005Co-Authors: Cory Pfeiffenberger, Jena Yamada, John G Flanagan, Georgia Woods, Tyler Cutforth, Rene C Renteria, David R Copenhagen, David A FeldheimAbstract:In mammals, retinal ganglion cell (RGC) projections initially intermingle and then segregate into a stereotyped pattern of eye-specific layers in the dorsal lateral geniculate nucleus (dLGN). Here we found that in mice deficient for Ephrin-A2, Ephrin-A3 and Ephrin-A5, eye-specific inputs segregated but the shape and location of eye-specific layers were profoundly disrupted. In contrast, mice that lacked correlated retinal activity did not segregate eye-specific inputs. Inhibition of correlated neural activity in Ephrin mutants led to overlapping retinal projections that were located in inappropriate regions of the dLGN. Thus, Ephrin-As and neural activity act together to control patterning of eye-specific retinogeniculate layers.
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Ephrin A2 and a5 influence patterning of normal and novel retinal projections to the thalamus conserved mapping mechanisms in visual and auditory thalamic targets
The Journal of Comparative Neurology, 2005Co-Authors: Charlene Ellsworth, David A Feldheim, John G Flanagan, Alvin W Lyckman, Mriganka SurAbstract:Sensory axons are targeted to modality-specific nuclei in the thalamus. Retinal ganglion cell axons project retinotopically to their principal thalamic target, the dorsal lateral geniculate nucleus (LGd), in a pattern likely dictated by the expression of molecular gradients in the LGd. Deafferenting the auditory thalamus induces retinal axons to innervate the medial geniculate nucleus (MGN). These retino-MGN projections also show retinotopic organization. Here we show that Ephrin-A2 and -A5, which are expressed in similar gradients in the MGN and LGd, can be used to pattern novel retinal projections in the MGN. As in the LGd, retinal axons from each eye terminate in discrete eye-specific zones in the MGN of rewired wild-type and Ephrin-A2/A5 knockout mice. However, ipsilateral eye axons, which arise from retinal regions of high EphA5 receptor expression and represent central visual field, terminate in markedly different ways in the two mice. In rewired wild-type mice, ipsilateral axons specifically avoid areas of high Ephrin expression in the MGN. In rewired Ephrin knockout mice, ipsilateral projections shift in location and spread more broadly, leading to an expanded representation of the ipsilateral eye in the MGN. Similarly, ipsilateral projections to the LGd in Ephrin knockout mice are shifted and are more widespread than in the LGd of wild-type mice. In the MGN, as in the LGd, terminations from the two eyes show little overlap even in the knockout mice, suggesting that local interocular segregation occurs regardless of other patterning determinants. Our data demonstrate that graded topographic labels, such as the Ephrins, can serve to shape multiple related aspects of afferent patterning, including topographic mapping and the extent and spread of eye-specific projections. Furthermore, when mapping labels and other cues are expressed in multiple target zones, novel projections are patterned according to rules that operate in their canonical targets. J. Comp. Neurol. 488:140–151, 2005. © 2005 Wiley-Liss, Inc.
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Ephrin-A2 and -A5 influence patterning of normal and novel retinal projections to the thalamus: conserved mapping mechanisms in visual and auditory thalamic targets.
The Journal of comparative neurology, 2005Co-Authors: Charlene Ellsworth, David A Feldheim, John G Flanagan, Alvin W Lyckman, Mriganka SurAbstract:Sensory axons are targeted to modality-specific nuclei in the thalamus. Retinal ganglion cell axons project retinotopically to their principal thalamic target, the dorsal lateral geniculate nucleus (LGd), in a pattern likely dictated by the expression of molecular gradients in the LGd. Deafferenting the auditory thalamus induces retinal axons to innervate the medial geniculate nucleus (MGN). These retino-MGN projections also show retinotopic organization. Here we show that Ephrin-A2 and -A5, which are expressed in similar gradients in the MGN and LGd, can be used to pattern novel retinal projections in the MGN. As in the LGd, retinal axons from each eye terminate in discrete eye-specific zones in the MGN of rewired wild-type and Ephrin-A2/A5 knockout mice. However, ipsilateral eye axons, which arise from retinal regions of high EphA5 receptor expression and represent central visual field, terminate in markedly different ways in the two mice. In rewired wild-type mice, ipsilateral axons specifically avoid areas of high Ephrin expression in the MGN. In rewired Ephrin knockout mice, ipsilateral projections shift in location and spread more broadly, leading to an expanded representation of the ipsilateral eye in the MGN. Similarly, ipsilateral projections to the LGd in Ephrin knockout mice are shifted and are more widespread than in the LGd of wild-type mice. In the MGN, as in the LGd, terminations from the two eyes show little overlap even in the knockout mice, suggesting that local interocular segregation occurs regardless of other patterning determinants. Our data demonstrate that graded topographic labels, such as the Ephrins, can serve to shape multiple related aspects of afferent patterning, including topographic mapping and the extent and spread of eye-specific projections. Furthermore, when mapping labels and other cues are expressed in multiple target zones, novel projections are patterned according to rules that operate in their canonical targets.
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Ephrin A2 reverse signaling negatively regulates neural progenitor proliferation and neurogenesis
Genes & Development, 2005Co-Authors: Johan Holmberg, John G Flanagan, Annika Armulik, Kirstenandre Senti, Karin Edoff, Kirsty L Spalding, Stefan Momma, Rob Cassidy, Jonas FrisénAbstract:The number of cells in an organ is regulated by mitogens and trophic factors that impinge on intrinsic determinants of proliferation and apoptosis. We here report the identification of an additional mechanism to control cell number in the brain: EphA7 induces Ephrin-A2 reverse signaling, which negatively regulates neural progenitor cell proliferation. Cells in the neural stem cell niche in the adult brain proliferate more and have a shorter cell cycle in mice lacking Ephrin-A2. The increased progenitor proliferation is accompanied by a higher number of cells in the olfactory bulb. Disrupting the interaction between Ephrin-A2 and EphA7 in the adult brain of wild-type mice disinhibits proliferation and results in increased neurogenesis. The identification of Ephrin-A2 and EphA7 as negative regulators of progenitor cell proliferation reveals a novel mechanism to control cell numbers in the brain.
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Domain-specific olivocerebellar projection regulated by the EphA-Ephrin-A interaction.
Development (Cambridge England), 2002Co-Authors: Kazuhiko Nishida, John G Flanagan, Masaru NakamotoAbstract:Neural maps in the vertebrate central nervous system often show discontinuously segregated, domain-to-domain patterns. However, the molecular mechanism that establishes such maps is not well understood. Here we show that in the chicken olivocerebellar system, EphA receptors and Ephrin-As are expressed with distinct levels and combinations in mapping domains. When Ephrin-A2 is retrovirally overexpressed in the cerebellum, the olivocerebellar map is disrupted, excluding axons with high receptor activity from ectopic expression domains. Conversely, overexpression of a truncated EphA3 receptor in the cerebellum reduces endogenous ligand activity to undetectable levels and causes aberrant mapping, with high receptor axons invading high ligand domains. In vitro, Ephrin-A2 inhibits outgrowth of inferior olive axons in a region-specific manner. These results suggest that Eph receptors and Ephrins constitute domain-specific positional information, and the spatially accurate receptor-ligand interaction is essential to guide inferior olive axons to their correct target domains.
Sarah A. Dunlop - One of the best experts on this subject based on the ideXlab platform.
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Functional Topography and Integration of the Contralateral and Ipsilateral Retinocollicular Projections of Ephrin-A−/− Mice
The Journal of neuroscience : the official journal of the Society for Neuroscience, 2008Co-Authors: Daniel J Haustead, Carole A. Bartlett, Sarah A. Dunlop, Genevieve T Clutton, Catherine A Arrese, Rachel M Sherrard, Sherralee Lukehurst, Jennifer RodgerAbstract:Topographically ordered projections are established by molecular guidance cues and refined by neuronal activity. Retinal input to a primary visual center, the superior colliculus (SC), is bilateral with a dense contralateral projection and a sparse ipsilateral one. Both projections are topographically organized, but in opposing anterior–posterior orientations. This arrangement provides functionally coherent input to each colliculus from the binocular visual field, supporting visual function. When guidance cues involved in contralateral topography (Ephrin-As) are absent, crossed retinal ganglion cell (RGC) axons form inappropriate terminations within the SC. However, the organization of the ipsilateral projection relative to the abnormal contralateral input remains unknown, as does the functional capacity of both projections. We show here that in Ephrin-A−/− mice, the SC contains an expanded, diffuse ipsilateral projection. Electrophysiological recording demonstrated that topography of visually evoked responses recorded from the contralateral superior colliculus of Ephrin-A−/− mice displayed similar functional disorder in all genotypes, contrasting with their different degrees of anatomical disorder. In contrast, ipsilateral responses were retinotopic in Ephrin-A2−/− but disorganized in Ephrin-A2/A5−/− mice. The lack of integration of binocular input resulted in specific visual deficits, which could be reversed by occlusion of one eye. The discrepancy between anatomical and functional topography in both the ipsilateral and contralateral projections implies suppression of inappropriately located terminals. Moreover, the misalignment of ipsilateral and contralateral visual information in Ephrin-A2/A5−/− mice suggests a role for Ephrin-As in integrating convergent visual inputs.
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Functional topography and integration of the contralateral and ipsilateral retinocollicular projections of Ephrin-A-/- mice.
Journal of Neuroscience, 2008Co-Authors: Daniel J Haustead, Carole A. Bartlett, Sarah A. Dunlop, Sherralee S Lukehurst, Genevieve T Clutton, Catherine A Arrese, Rachel M Sherrard, Jennifer RodgerAbstract:Topographically ordered projections are established by molecular guidance cues and refined by neuronal activity. Retinal input to a primary visual center, the superior colliculus (SC), is bilateral with a dense contralateral projection and a sparse ipsilateral one. Both projections are topographically organized, but in opposing anterior-posterior orientations. This arrangement provides functionally coherent input to each colliculus from the binocular visual field, supporting visual function. When guidance cues involved in contralateral topography (Ephrin-As) are absent, crossed retinal ganglion cell (RGC) axons form inappropriate terminations within the SC. However, the organization of the ipsilateral projection relative to the abnormal contralateral input remains unknown, as does the functional capacity of both projections. We show here that in Ephrin-A(-/-) mice, the SC contains an expanded, diffuse ipsilateral projection. Electrophysiological recording demonstrated that topography of visually evoked responses recorded from the contralateral superior colliculus of Ephrin-A(-/-) mice displayed similar functional disorder in all genotypes, contrasting with their different degrees of anatomical disorder. In contrast, ipsilateral responses were retinotopic in Ephrin-A2(-/-) but disorganized in Ephrin-A2/A5(-/-) mice. The lack of integration of binocular input resulted in specific visual deficits, which could be reversed by occlusion of one eye. The discrepancy between anatomical and functional topography in both the ipsilateral and contralateral projections implies suppression of inappropriately located terminals. Moreover, the misalignment of ipsilateral and contralateral visual information in Ephrin-A2/A5(-/-) mice suggests a role for Ephrin-As in integrating convergent visual inputs.
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EphA5 and Ephrin-A2 expression during optic nerve regeneration : a 'two edged sword'
The European journal of neuroscience, 2007Co-Authors: A.c.e. Symonds, Carole A. Bartlett, Sarah A. Dunlop, Lyn Beazley, Carolyn E. King, Y. Sauve, Raymond D. Lund, Jennifer RodgerAbstract:During development, gradients of EphA receptors (nasal(low)-temporal(high)) and their ligands Ephrin-As (rostral(low)-caudal(high)) are involved in establishing topography between retinal ganglion cells (RGCs) and the superior colliculus (SC). EphA5-expressing RGC axons are repulsed by Ephrin-A2-expressing SC neurones. In adult rats RGCs maintain graded EphA5 expression but Ephrin-A2 expression is down-regulated in the SC to a weak gradient. At 1 month after optic nerve transection, EphA5 expression is reduced in the few remaining RGCs and is no longer graded; by contrast, SC Ephrin-A2 is up-regulated to a rostral(low)-caudal(high) gradient. Here we examined expression in adult rat 1 month after bridging the retina and SC with a peripheral nerve graft, a procedure that enhances RGC survival and permits RGC axon regeneration. Double labelling with cell markers revealed preservation of a nasal(low)-temporal(high) EphA5 gradient in RGCs and establishment of a rostral(low)-caudal(high) Ephrin-A2 gradient within neurones of the SC. The results suggest a potential for guidance cues to restore the topography of RGC axons in the SC. However, high Ephrin-A2 levels were also found in astrocytes surrounding the peripheral nerve graft insertion site. The repulsive Ephrin-A2 environment offers at least a partial explanation for the observation that only a limited number of RGC axons can exit the graft to enter target central nervous system tissue.
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Eph/Ephrin expression in the adult rat visual system following localized retinal lesions : localized and transneuronal up-regulation in the retina and superior colliculus
European Journal of Neuroscience, 2005Co-Authors: Jennifer Rodger, A.c.e. Symonds, J. Springbett, Carole A. Bartlett, Lyn Beazley, W. Y. Shen, Piroska E. Rakoczy, Sarah A. DunlopAbstract:Following unilateral optic nerve section in adult PVG hooded rat, the axon guidance cue Ephrin-A2 is up-regulated in caudal but not rostral superior colliculus (SC) and the EphA5 receptor is down-regulated in axotomised retinal ganglion cells (RGCs). Changes occur bilaterally despite the retino-collicular projection being mostly crossed. Here we investigate the dynamics of Eph/Ephrin expression using in situ hybridization and semi-quantitative immunohistochemistry after localized retinal lesions. Unilateral krypton laser lesions to dorso-nasal retina ablated contralaterally projecting RGCs (DN group); ventro-temporal lesions ablated contralaterally and ipsilaterally projecting RGCs (VT group). Lesions of the entire retina served as controls (Total group). Results are compared to normal animals in which tectal Ephrin-A2 and retinal EphA5 are expressed, respectively, as shallow ascending rostro-caudal and naso-temporal gradients. In both SCs of DN and Total groups, tectal Ephrin-A2 was up-regulated caudally; in the VT group, expression remained normal bilaterally. Unilateral collicular ablation indicated that bilateral changes in Ephrin-A2 expression are mediated via intercollicular pathways. EphA5 expression in the VT group was elevated in the intact nasal region of experimental retinae. For each experimental group, EphA5 expression was also elevated in nasal retina of the opposite eye, resulting in uniform expression across the naso-temporal axis. Up-regulation of Ephrin-A2 in caudal, but not rostral, SC suggests the enhancement of developmental positional information as a result of injury. Bilateral increases in retinal EphA5 expression demonstrate that signals for up-regulation operate interocularly. The study demonstrates that signals regulating guidance cue expression are both localized and relayed transneuronally.
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Characterisation of tectal Ephrin-A2 expression during optic nerve regeneration in goldfish : implications for restoration of topography
Experimental neurology, 2004Co-Authors: Carolyn E. King, Carole A. Bartlett, Sarah A. Dunlop, Jennifer Rodger, Richard Lacey, Lyn BeazleyAbstract:EphA receptors and their ligands the Ephrin-As, expressed as retinal and tectal gradients, are required for the development of retino-tectal topography [Neuron 25 (2000) 563] and its restoration during goldfish optic nerve regeneration [Mol. Cell. Neurosci. 25 (2004) 56]. We have reported previously that, during regeneration, a transient EphA3/A5 gradient is formed by differential expression across the entire retinal ganglion cell (RGC) population [Neurosci. Abs. 33 (2003) 358.2; Exp. Neurol. 183 (2003) 593]. In retino-recipient tectal layers, Ephrin-A2 is normally expressed by only a sub-population of cells, but during regeneration, there is a graded increase with more expressing cells caudally than rostrally [Exp. Neurol. 166 (2000) 196]. Here, we examine the characteristics of tectal Ephrin-A2 expression during regeneration. We report that the level of Ephrin-A2 expression is comparable for all Ephrin-A2-positive cells in normal animals and during regeneration. Using double-labelling immunohistochemistry for Ephrin-A2 and specific cell markers (NeuN for neurons, GA5 for astrocytes, NN-1 for microglia/endothelial cells and 6D2 for oligodendrocytes), we demonstrate that Ephrin-A2-expressing cells, as in normal animals, are exclusively neuronal. Moreover, double labelling with BrdU showed that Ephrin-A2 is expressed in resident cells and not those generated during optic nerve regeneration [Brain Res. 854 (2000) 178, 153 (1978) 345].
Lyn Beazley - One of the best experts on this subject based on the ideXlab platform.
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EphA5 and Ephrin-A2 expression during optic nerve regeneration : a 'two edged sword'
The European journal of neuroscience, 2007Co-Authors: A.c.e. Symonds, Carole A. Bartlett, Sarah A. Dunlop, Lyn Beazley, Carolyn E. King, Y. Sauve, Raymond D. Lund, Jennifer RodgerAbstract:During development, gradients of EphA receptors (nasal(low)-temporal(high)) and their ligands Ephrin-As (rostral(low)-caudal(high)) are involved in establishing topography between retinal ganglion cells (RGCs) and the superior colliculus (SC). EphA5-expressing RGC axons are repulsed by Ephrin-A2-expressing SC neurones. In adult rats RGCs maintain graded EphA5 expression but Ephrin-A2 expression is down-regulated in the SC to a weak gradient. At 1 month after optic nerve transection, EphA5 expression is reduced in the few remaining RGCs and is no longer graded; by contrast, SC Ephrin-A2 is up-regulated to a rostral(low)-caudal(high) gradient. Here we examined expression in adult rat 1 month after bridging the retina and SC with a peripheral nerve graft, a procedure that enhances RGC survival and permits RGC axon regeneration. Double labelling with cell markers revealed preservation of a nasal(low)-temporal(high) EphA5 gradient in RGCs and establishment of a rostral(low)-caudal(high) Ephrin-A2 gradient within neurones of the SC. The results suggest a potential for guidance cues to restore the topography of RGC axons in the SC. However, high Ephrin-A2 levels were also found in astrocytes surrounding the peripheral nerve graft insertion site. The repulsive Ephrin-A2 environment offers at least a partial explanation for the observation that only a limited number of RGC axons can exit the graft to enter target central nervous system tissue.
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Graded Ephrin-A2 expression in the developing hamster superior colliculus
Experimental brain research, 2006Co-Authors: Sherralee Lukehurst, Lyn Beazley, Carolyn E. King, David Tay, Jennifer RodgerAbstract:During development, Ephrin gradients guide retinal ganglion cell axons to their appropriate topographic locations in the superior colliculus (SC). Expression of Ephrin-A2, assessed immunohistochemically in the developing hamster SC, revealed a rostrallow to caudalhigh gradient that is most prominent at postnatal days (P)4 and P7 when topography is established. Double-labelling immunohistochemistry for Ephrin-A2 and cell specific markers revealed that Ephrin-A2 is expressed exclusively by a subset of neurons. The expression pattern has implications for mechanisms underlying establishment of topography during development and following injury.
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Eph/Ephrin expression in the adult rat visual system following localized retinal lesions : localized and transneuronal up-regulation in the retina and superior colliculus
European Journal of Neuroscience, 2005Co-Authors: Jennifer Rodger, A.c.e. Symonds, J. Springbett, Carole A. Bartlett, Lyn Beazley, W. Y. Shen, Piroska E. Rakoczy, Sarah A. DunlopAbstract:Following unilateral optic nerve section in adult PVG hooded rat, the axon guidance cue Ephrin-A2 is up-regulated in caudal but not rostral superior colliculus (SC) and the EphA5 receptor is down-regulated in axotomised retinal ganglion cells (RGCs). Changes occur bilaterally despite the retino-collicular projection being mostly crossed. Here we investigate the dynamics of Eph/Ephrin expression using in situ hybridization and semi-quantitative immunohistochemistry after localized retinal lesions. Unilateral krypton laser lesions to dorso-nasal retina ablated contralaterally projecting RGCs (DN group); ventro-temporal lesions ablated contralaterally and ipsilaterally projecting RGCs (VT group). Lesions of the entire retina served as controls (Total group). Results are compared to normal animals in which tectal Ephrin-A2 and retinal EphA5 are expressed, respectively, as shallow ascending rostro-caudal and naso-temporal gradients. In both SCs of DN and Total groups, tectal Ephrin-A2 was up-regulated caudally; in the VT group, expression remained normal bilaterally. Unilateral collicular ablation indicated that bilateral changes in Ephrin-A2 expression are mediated via intercollicular pathways. EphA5 expression in the VT group was elevated in the intact nasal region of experimental retinae. For each experimental group, EphA5 expression was also elevated in nasal retina of the opposite eye, resulting in uniform expression across the naso-temporal axis. Up-regulation of Ephrin-A2 in caudal, but not rostral, SC suggests the enhancement of developmental positional information as a result of injury. Bilateral increases in retinal EphA5 expression demonstrate that signals for up-regulation operate interocularly. The study demonstrates that signals regulating guidance cue expression are both localized and relayed transneuronally.
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Expression profiles suggest a role for Pax7 in the establishment of tectal polarity and map refinement
Experimental Brain Research, 2004Co-Authors: Meghan Thomas, Lyn Beazley, Stan Lazic, Melanie ZimanAbstract:The role for Pax7 in establishing tectal polarity and map refinement was authenticated by gene expression studies in vivo and in vitro. Throughout development (stages E2–E12 were examined) a rostral^low-caudal^high and dorsal^high-ventral^low Pax7 expression gradient was detected immunohistochemically in the chick optic tectum, indicating a role for Pax7 in establishing tectal polarity. Chick retino-recipient tectal cells positive for Pax7 also co-expressed Ephrin-A2 , a molecule involved in the establishment and refinement of the retinotopic map. In vitro, PAX7 up-regulated Ephrin-A2 when transfected into undifferentiated P19 cells; cells became negative for both Pax7 and Ephrin-A2 protein following treatment with anti-sense oligonucleotides. These results suggest that in addition to being involved in the early establishment of tectal polarity, Pax7 plays a later role in retino-tectal map formation and refinement.
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Characterisation of tectal Ephrin-A2 expression during optic nerve regeneration in goldfish : implications for restoration of topography
Experimental neurology, 2004Co-Authors: Carolyn E. King, Carole A. Bartlett, Sarah A. Dunlop, Jennifer Rodger, Richard Lacey, Lyn BeazleyAbstract:EphA receptors and their ligands the Ephrin-As, expressed as retinal and tectal gradients, are required for the development of retino-tectal topography [Neuron 25 (2000) 563] and its restoration during goldfish optic nerve regeneration [Mol. Cell. Neurosci. 25 (2004) 56]. We have reported previously that, during regeneration, a transient EphA3/A5 gradient is formed by differential expression across the entire retinal ganglion cell (RGC) population [Neurosci. Abs. 33 (2003) 358.2; Exp. Neurol. 183 (2003) 593]. In retino-recipient tectal layers, Ephrin-A2 is normally expressed by only a sub-population of cells, but during regeneration, there is a graded increase with more expressing cells caudally than rostrally [Exp. Neurol. 166 (2000) 196]. Here, we examine the characteristics of tectal Ephrin-A2 expression during regeneration. We report that the level of Ephrin-A2 expression is comparable for all Ephrin-A2-positive cells in normal animals and during regeneration. Using double-labelling immunohistochemistry for Ephrin-A2 and specific cell markers (NeuN for neurons, GA5 for astrocytes, NN-1 for microglia/endothelial cells and 6D2 for oligodendrocytes), we demonstrate that Ephrin-A2-expressing cells, as in normal animals, are exclusively neuronal. Moreover, double labelling with BrdU showed that Ephrin-A2 is expressed in resident cells and not those generated during optic nerve regeneration [Brain Res. 854 (2000) 178, 153 (1978) 345].