The Experts below are selected from a list of 306 Experts worldwide ranked by ideXlab platform
Carol A Mason - One of the best experts on this subject based on the ideXlab platform.
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retinal axon growth at the Optic Chiasm to cross or not to cross
Annual Review of Neuroscience, 2008Co-Authors: Timothy J Petros, Alexandra Rebsam, Carol A MasonAbstract:At the Optic Chiasm, retinal ganglion cell axons from each eye converge and segregate into crossed and uncrossed projections, a pattern critical for binocular vision. Here, we review recent findings on Optic Chiasm development, highlighting the specific transcription factors and guidance cues that implement retinal axon divergence into crossed and uncrossed pathways. Although mechanisms underlying the formation of the uncrossed projection have been identified, the means by which retinal axons are guided across the midline are still unclear. In addition to directives provided by transcription factors and receptors in the retina, gene expression in the ventral diencephalon influences Chiasm formation. Throughout this review, we compare guidance mechanisms at the Optic Chiasm with those in other midline models and highlight unanswered questions both for retinal axon growth and axon guidance in general.
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zic2 promotes axonal divergence at the Optic Chiasm midline by ephb1 dependent and independent mechanisms
Development, 2008Co-Authors: Cristina Garciafrigola, Carol A Mason, Maria Isabel Carreres, Celia Vegar, Eloísa HerreraAbstract:Axons of retinal ganglion cells (RGCs) make a divergent choice at the Optic Chiasm to cross or avoid the midline in order to project to ipsilateral and contralateral targets, thereby establishing the binocular visual pathway. The zinc-finger transcription factor Zic2 and a member of the Eph family of receptor tyrosine kinases, EphB1, are both essential for proper development of the ipsilateral projection at the mammalian Optic Chiasm midline. Here, we demonstrate in mouse by functional experiments in vivo that Zic2 is not only required but is also sufficient to change the trajectory of RGC axons from crossed to uncrossed. In addition, our results reveal that this transcription factor regulates the expression of EphB1 in RGCs and also suggest the existence of an additional EphB1-independent pathway controlled by Zic2 that contributes to retinal axon divergence at the midline.
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foxd1 is required for proper formation of the Optic Chiasm
Development, 2004Co-Authors: Eloísa Herrera, Scott E Williams, Riva C Marcus, Suzanne Li, Lynda Erskine, Carol A MasonAbstract:In animals with binocular vision, retinal ganglion cell (RGC) axons from each eye sort in the developing ventral diencephalon to project to ipsi- or contralateral targets, thereby forming the Optic Chiasm. Ipsilaterally projecting axons arise from the ventrotemporal (VT) retina and contralaterally projecting axons primarily from the other retinal quadrants. The winged helix transcription factor Foxd1 (previously known as BF-2, Brain Factor 2) is expressed in VT retina, as well as in the ventral diencephalon during the formation of the Optic Chiasm. We report here that in embryos lacking Foxd1, both retinal development and Chiasm morphogenesis are disrupted. In the Foxd1 deficient retina, proteins designating the ipsilateral projection, such as Zic2 and EphB1, are missing, and the domain of Foxg1 (BF-1) expands from nasal retina into the VT crescent. In retina-Chiasm co-cultures, VT RGCs from Foxd1 deficient retina are not repulsed by Chiasm cells, and in vivo many VT RGCs aberrantly project contralaterally. However, even though the ipsilateral program is lost in the retina, a larger than normal uncrossed component develops in Foxd1 deficient embryos. Chiasm defects include axon stalling in the Chiasm and a reduction in the total number of RGCs projecting to the Optic tract. In addition, in the Foxd1 deficient ventral diencephalon, Foxg1 invades the Foxd1 domain, Zic2 and Islet1 expression are minimized, and Slit2 prematurely expands, changes that could contribute to axon projection errors. Thus, Foxd1 plays a dual role in the establishment of the binocular visual pathways: first, in specification of the VT retina, acting upstream of proteins directing the ipsilateral pathway; and second, in the patterning of the developing ventral diencephalon where the Optic Chiasm forms.
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the Optic Chiasm as a midline choice point
Current Opinion in Neurobiology, 2004Co-Authors: Scott E Williams, Carol A Mason, Eloísa HerreraAbstract:Abstract The mouse Optic Chiasm is a model for axon guidance at the midline and for analyzing how binocular vision is patterned. Recent work has identified several molecular players that influence the binary decision that retinal ganglion cells make at the Optic Chiasm, to either cross or avoid the midline. An ephrin-B localized to the midline, together with an EphB receptor and a zinc-finger transcription factor expressed exclusively in the ventrotemporal retina where ipsilaterally projecting retinal ganglion cells are located, comprise a molecular program for the uncrossed pathway. In addition, the mechanisms for axon divergence in the Optic Chiasm are discussed in the context of other popular models for midline axon guidance.
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glia neurons and axon pathfinding during Optic Chiasm development
Current Opinion in Neurobiology, 1997Co-Authors: Carol A Mason, David W SretavanAbstract:Abstract The importance of vision in the behavior of animals, from invertebrates to primates, has led to a good deal of interest in how projection neurons in the retina make specific connections with targets in the brain. Recent research has focused on the cellular interactions occurring between retinal ganglion cell (RGC) axons and specific glial and neuronal populations in the embryonic brain during formation of the mouse Optic Chiasm. These interactions appear to be involved both in determining the position of the Optic Chiasm on the ventral diencephalon (presumptive hypothalamus) and in ipsilateral and contralateral RGC axon pathfinding, developmental events fundamental to binocular vision in the adult animal.
Eloísa Herrera - One of the best experts on this subject based on the ideXlab platform.
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zic2 promotes axonal divergence at the Optic Chiasm midline by ephb1 dependent and independent mechanisms
Development, 2008Co-Authors: Cristina Garciafrigola, Carol A Mason, Maria Isabel Carreres, Celia Vegar, Eloísa HerreraAbstract:Axons of retinal ganglion cells (RGCs) make a divergent choice at the Optic Chiasm to cross or avoid the midline in order to project to ipsilateral and contralateral targets, thereby establishing the binocular visual pathway. The zinc-finger transcription factor Zic2 and a member of the Eph family of receptor tyrosine kinases, EphB1, are both essential for proper development of the ipsilateral projection at the mammalian Optic Chiasm midline. Here, we demonstrate in mouse by functional experiments in vivo that Zic2 is not only required but is also sufficient to change the trajectory of RGC axons from crossed to uncrossed. In addition, our results reveal that this transcription factor regulates the expression of EphB1 in RGCs and also suggest the existence of an additional EphB1-independent pathway controlled by Zic2 that contributes to retinal axon divergence at the midline.
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Genetics and development of the Optic Chiasm.
Frontiers in Bioscience, 2008Co-Authors: Eloísa Herrera, Cristina García-frigolaAbstract:In animals with binocular vision, retinal fibers either project across the midline or they remain on the same side of the ventral diencephalon, forming an X-shaped commissure known as the Optic Chiasm. The correct formation of the Optic Chiasm during development is essential to establish a fully functional visual system. Visual dysfunction associated with axonal misrouting at the Optic Chiasm has been described in albino individuals and in patients with non-decussating retinal-fugal fiber syndrome. Although little is known about the causes of retinal misrouting in these conditions, the molecular mechanisms responsible for the formation of the Optic Chiasm are beginning to be elucidated in vertebrates. This review focuses on our current knowledge of how the Optic Chiasm forms, which will hopefully help us to better understand these congenital anomalies.
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foxd1 is required for proper formation of the Optic Chiasm
Development, 2004Co-Authors: Eloísa Herrera, Scott E Williams, Riva C Marcus, Suzanne Li, Lynda Erskine, Carol A MasonAbstract:In animals with binocular vision, retinal ganglion cell (RGC) axons from each eye sort in the developing ventral diencephalon to project to ipsi- or contralateral targets, thereby forming the Optic Chiasm. Ipsilaterally projecting axons arise from the ventrotemporal (VT) retina and contralaterally projecting axons primarily from the other retinal quadrants. The winged helix transcription factor Foxd1 (previously known as BF-2, Brain Factor 2) is expressed in VT retina, as well as in the ventral diencephalon during the formation of the Optic Chiasm. We report here that in embryos lacking Foxd1, both retinal development and Chiasm morphogenesis are disrupted. In the Foxd1 deficient retina, proteins designating the ipsilateral projection, such as Zic2 and EphB1, are missing, and the domain of Foxg1 (BF-1) expands from nasal retina into the VT crescent. In retina-Chiasm co-cultures, VT RGCs from Foxd1 deficient retina are not repulsed by Chiasm cells, and in vivo many VT RGCs aberrantly project contralaterally. However, even though the ipsilateral program is lost in the retina, a larger than normal uncrossed component develops in Foxd1 deficient embryos. Chiasm defects include axon stalling in the Chiasm and a reduction in the total number of RGCs projecting to the Optic tract. In addition, in the Foxd1 deficient ventral diencephalon, Foxg1 invades the Foxd1 domain, Zic2 and Islet1 expression are minimized, and Slit2 prematurely expands, changes that could contribute to axon projection errors. Thus, Foxd1 plays a dual role in the establishment of the binocular visual pathways: first, in specification of the VT retina, acting upstream of proteins directing the ipsilateral pathway; and second, in the patterning of the developing ventral diencephalon where the Optic Chiasm forms.
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the Optic Chiasm as a midline choice point
Current Opinion in Neurobiology, 2004Co-Authors: Scott E Williams, Carol A Mason, Eloísa HerreraAbstract:Abstract The mouse Optic Chiasm is a model for axon guidance at the midline and for analyzing how binocular vision is patterned. Recent work has identified several molecular players that influence the binary decision that retinal ganglion cells make at the Optic Chiasm, to either cross or avoid the midline. An ephrin-B localized to the midline, together with an EphB receptor and a zinc-finger transcription factor expressed exclusively in the ventrotemporal retina where ipsilaterally projecting retinal ganglion cells are located, comprise a molecular program for the uncrossed pathway. In addition, the mechanisms for axon divergence in the Optic Chiasm are discussed in the context of other popular models for midline axon guidance.
Jun Wang - One of the best experts on this subject based on the ideXlab platform.
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The growth‐inhibitory protein Nogo is involved in midline routing of axons in the mouse Optic Chiasm
Journal of Neuroscience Research, 2008Co-Authors: Jun Wang, Chungkit Chan, Jeremy S H Taylor, Sunon ChanAbstract:We have investigated the role of Nogo, a protein that inhibits regenerating axons in the adult central nervous system, on axon guidance in the developing Optic Chiasm of mouse embryos. Nogo protein is expressed by radial glia in the midline within the Optic Chiasm where uncrossed axons turn, and the Nogo receptor (NgR) is expressed on retinal neurites and growth cones. In vitro neurite outgrowth from both dorsonasal and ventrotemporal retina was inhibited by Nogo protein, and this inhibition was abolished by blocking NgR activity. In slice cultures of the Optic pathway, blocking NgR with a peptide antagonist produced significant reduction in the uncrossed projection but had no effect on the crossing axons. This result was confirmed by treating cultures with an anti-Nogo functional blocking antibody. In vitro coculture assays of retina and Optic Chiasm showed that NgR was selectively reduced on neurites and growth cones from dorsonasal retina when they contacted Chiasm cells, but not on those from ventrotemporal retina. These findings provide evidence that Nogo signaling is involved in directing the growth of axons in the mouse Optic Chiasm and that this process relies on a differential regulation of NgR on axons from the dorsonasal and ventrotemporal retina.
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the growth inhibitory protein nogo is involved in midline routing of axons in the mouse Optic Chiasm
Journal of Neuroscience Research, 2008Co-Authors: Chungkit Chan, Jun Wang, Jeremy S H Taylor, Sunon ChanAbstract:We have investigated the role of Nogo, a protein that inhibits regenerating axons in the adult central nervous system, on axon guidance in the developing Optic Chiasm of mouse embryos. Nogo protein is expressed by radial glia in the midline within the Optic Chiasm where uncrossed axons turn, and the Nogo receptor (NgR) is expressed on retinal neurites and growth cones. In vitro neurite outgrowth from both dorsonasal and ventrotemporal retina was inhibited by Nogo protein, and this inhibition was abolished by blocking NgR activity. In slice cultures of the Optic pathway, blocking NgR with a peptide antagonist produced significant reduction in the uncrossed projection but had no effect on the crossing axons. This result was confirmed by treating cultures with an anti-Nogo functional blocking antibody. In vitro coculture assays of retina and Optic Chiasm showed that NgR was selectively reduced on neurites and growth cones from dorsonasal retina when they contacted Chiasm cells, but not on those from ventrotemporal retina. These findings provide evidence that Nogo signaling is involved in directing the growth of axons in the mouse Optic Chiasm and that this process relies on a differential regulation of NgR on axons from the dorsonasal and ventrotemporal retina. © 2008 Wiley-Liss, Inc.
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enzymatic removal of hyaluronan affects routing of axons in the mouse Optic Chiasm
Neuroreport, 2007Co-Authors: Chungkit Chan, Jun Wang, Sunon ChanAbstract:: Perturbations of interaction of hyaluronan (HA) with its receptor CD44 cause multiple errors in axon routing at the mouse Optic Chiasm. To investigate this interaction further on the Chiasm routing, we studied the axon routing after enzymatic removal of HA from slice preparations of the Optic pathway. Hyaluronidase treatment produced an obvious reduction in midline crossing of the first generated axons in E13 Chiasms, but had no influence on routing ofthe uncrossed axons in E15 and E16 slices. These findings support a direct role of HA, acting probably through CD44, on axon decussation during early phase of Chiasm development, but argue against a direct function of HA on the turning of uncrossed axons in the mouse Optic Chiasm.
Sunon Chan - One of the best experts on this subject based on the ideXlab platform.
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The growth‐inhibitory protein Nogo is involved in midline routing of axons in the mouse Optic Chiasm
Journal of Neuroscience Research, 2008Co-Authors: Jun Wang, Chungkit Chan, Jeremy S H Taylor, Sunon ChanAbstract:We have investigated the role of Nogo, a protein that inhibits regenerating axons in the adult central nervous system, on axon guidance in the developing Optic Chiasm of mouse embryos. Nogo protein is expressed by radial glia in the midline within the Optic Chiasm where uncrossed axons turn, and the Nogo receptor (NgR) is expressed on retinal neurites and growth cones. In vitro neurite outgrowth from both dorsonasal and ventrotemporal retina was inhibited by Nogo protein, and this inhibition was abolished by blocking NgR activity. In slice cultures of the Optic pathway, blocking NgR with a peptide antagonist produced significant reduction in the uncrossed projection but had no effect on the crossing axons. This result was confirmed by treating cultures with an anti-Nogo functional blocking antibody. In vitro coculture assays of retina and Optic Chiasm showed that NgR was selectively reduced on neurites and growth cones from dorsonasal retina when they contacted Chiasm cells, but not on those from ventrotemporal retina. These findings provide evidence that Nogo signaling is involved in directing the growth of axons in the mouse Optic Chiasm and that this process relies on a differential regulation of NgR on axons from the dorsonasal and ventrotemporal retina.
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the growth inhibitory protein nogo is involved in midline routing of axons in the mouse Optic Chiasm
Journal of Neuroscience Research, 2008Co-Authors: Chungkit Chan, Jun Wang, Jeremy S H Taylor, Sunon ChanAbstract:We have investigated the role of Nogo, a protein that inhibits regenerating axons in the adult central nervous system, on axon guidance in the developing Optic Chiasm of mouse embryos. Nogo protein is expressed by radial glia in the midline within the Optic Chiasm where uncrossed axons turn, and the Nogo receptor (NgR) is expressed on retinal neurites and growth cones. In vitro neurite outgrowth from both dorsonasal and ventrotemporal retina was inhibited by Nogo protein, and this inhibition was abolished by blocking NgR activity. In slice cultures of the Optic pathway, blocking NgR with a peptide antagonist produced significant reduction in the uncrossed projection but had no effect on the crossing axons. This result was confirmed by treating cultures with an anti-Nogo functional blocking antibody. In vitro coculture assays of retina and Optic Chiasm showed that NgR was selectively reduced on neurites and growth cones from dorsonasal retina when they contacted Chiasm cells, but not on those from ventrotemporal retina. These findings provide evidence that Nogo signaling is involved in directing the growth of axons in the mouse Optic Chiasm and that this process relies on a differential regulation of NgR on axons from the dorsonasal and ventrotemporal retina. © 2008 Wiley-Liss, Inc.
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enzymatic removal of hyaluronan affects routing of axons in the mouse Optic Chiasm
Neuroreport, 2007Co-Authors: Chungkit Chan, Jun Wang, Sunon ChanAbstract:: Perturbations of interaction of hyaluronan (HA) with its receptor CD44 cause multiple errors in axon routing at the mouse Optic Chiasm. To investigate this interaction further on the Chiasm routing, we studied the axon routing after enzymatic removal of HA from slice preparations of the Optic pathway. Hyaluronidase treatment produced an obvious reduction in midline crossing of the first generated axons in E13 Chiasms, but had no influence on routing ofthe uncrossed axons in E15 and E16 slices. These findings support a direct role of HA, acting probably through CD44, on axon decussation during early phase of Chiasm development, but argue against a direct function of HA on the turning of uncrossed axons in the mouse Optic Chiasm.
David W Sretavan - One of the best experts on this subject based on the ideXlab platform.
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glia neurons and axon pathfinding during Optic Chiasm development
Current Opinion in Neurobiology, 1997Co-Authors: Carol A Mason, David W SretavanAbstract:Abstract The importance of vision in the behavior of animals, from invertebrates to primates, has led to a good deal of interest in how projection neurons in the retina make specific connections with targets in the brain. Recent research has focused on the cellular interactions occurring between retinal ganglion cell (RGC) axons and specific glial and neuronal populations in the embryonic brain during formation of the mouse Optic Chiasm. These interactions appear to be involved both in determining the position of the Optic Chiasm on the ventral diencephalon (presumptive hypothalamus) and in ipsilateral and contralateral RGC axon pathfinding, developmental events fundamental to binocular vision in the adult animal.
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disruption of retinal axon ingrowth by ablation of embryonic mouse Optic Chiasm neurons
Science, 1995Co-Authors: David W Sretavan, E Pure, M W Siegel, Louis F ReichardtAbstract:Mouse retinal ganglion cell axons growing from the eye encounter embryonic neurons at the future site of the Optic Chiasm. After in vivo ablation of these Chiasm neurons with a monoclonal antibody and complement, retinal axons did not cross the midline and stalled at approximately the entry site into the Chiasm region. Thus, in the mouse, the presence of early-generated neurons that reside at the site of the future Chiasm is required for formation of the Optic Chiasm by retinal ganglion cell axons.
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specific routing of retinal ganglion cell axons at the mammalian Optic Chiasm during embryonic development
The Journal of Neuroscience, 1990Co-Authors: David W SretavanAbstract:During development of the mammalian CNS, axons encounter multiple pathway choices on their way to central target structures. A major pathway branch point in the visual system occurs at the Optic Chiasm, where retinal ganglion cell axons may either enter the ipsilateral or the contralateral Optic tract. To investigate whether embryonic mouse retinal ganglion cell axons, upon reaching the Optic Chiasm, selectively grow into the correct pathway, developing retinal ganglion cells were retrogradely labeled using either 1,1′dioctadecyl- 3,3,3′,3′tetramethylindocarbocyanine perchlorate (Dil) or fluorescent microspheres placed into the Optic tract on one side. The distribution of ipsilaterally and contralaterally projecting ganglion cells in the embryo was then examined and compared to that of the adult animal. Results show that axon routing at the Chiasm is already extremely adult- like as early as embryonic day 15 (E15), shortly after retinal axons arrive at the Chiasm. [Retinal ganglion cell neurogenesis = E11-E18 (Drager, 1985); birth = E21.] Throughout the development of this pathway, routing errors are infrequent and are on the order of only about 3–8/1000 retinal ganglion cells. Thus, embryonic retinal ganglion cell axons do not project randomly at the Optic Chiasm but instead appear to be highly specific in their choice of pathway. To learn how correct pathway choices are made, retinal axons were retrogradely labeled with Dil and their trajectories at the Optic Chiasm were reconstructed. Results show that ipsilaterally and contralaterally projecting axons are highly intermixed as they enter the Chiasm region but selectively grow into the correct pathway. For example, a contralaterally projecting axon near the entrance of the ipsilateral Optic tract will turn and bypass this pathway and grow towards the midline to head into the contralateral Optic tract. Similarly, axons far away from the ipsilateral Optic tract frequently turn abruptly at right angles to enter the ipsilateral tract, directly crossing over contralaterally projecting axons heading to the opposite side. The sorting out of intermixed ipsilaterally and contralaterally projecting retinal axons into the appropriate Optic tracts strongly suggests the presence of specific guidance cues at the Optic Chiasm during embryonic development. Together, results from this study demonstrate that the pattern of axon projection at the adult mammalian Optic Chiasm is gradually built upon a highly specific pattern of axon routing laid down early during development.
