Multiple ephrins regulate hippocampal neurite outgrowth

Brownlee, Heather; Gao, Pan; Frisén, Jonas; Dreyfus, Cheryl F.; Zhou, Ran; Black, Ira B.

doi:10.1002/1096-9861(20000918)425:2<315::aid-cne12>3.0.co;2-#

Cited by 26 publications

(16 citation statements)

References 22 publications

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“…Cortical interneurons arising from the MGE migrate along distinct routes towards the cortex, thereby avoiding the striatal anlage (StrA), which represents a non-target territory for cortical interneurons. We found that ephrin-A3, a member of the A-ephrins that acts as a repellent in other regions of the developing nervous system, [31][32][33] proposed that Slit1/Robo interactions are involved in regulating the migration from the MGE by a repulsive activity. Indeed, Slit1 has been shown to repel subpallial GABAergic neurons in vitro.…”

Section: Resultsmentioning

confidence: 99%

Ephrins guide migrating cortical interneurons in the basal telencephalon

Rudolph

Zimmer

Steinecke

et al. 2010

Cell Adhesion & Migration

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Cortical interneurons are born in the proliferative zones of the ganglionic eminences in the subpallium and migrate to the developing cortex along well-defined tangential routes. The mechanisms regulating interneuron migration are not completely understood. Here we examine the role of class-A members of the Eph/ephrin system in directing the migration of interneurons. In situ hybridizations demonstrated that ephrin-A3 is expressed in the developing striatum, an area that is strictly avoided by migrating cortical interneurons in vivo, which express the EphA4 receptor. We then examined interneuron migration in grafting experiments, where explants of the medial ganglionic eminence (MGE) from enhanced green fluorescent protein-expressing transgenic mice were homotopically grafted into host slices from wildtype littermate embryos. After blocking ephrin-A ligands, many interneurons invaded the striatal anlage. Moreover, stripe assay experiments revealed that ephrin-A3 acts as a repellent cue for neurons from the medial ganglionic eminence. Downregulation of the EphA4 receptor via siRNA transfection reduced the repulsive effect of ephrin-A3, indicating that EphA4 mediates at least in part the repulsive effect of ephrin-A3 on these cells. Together, these results suggest that ephrin-A3 acts as a repulsive cue that restricts cortical interneurons from entering inappropriate regions and thus contributes to define the migratory route of cortical interneurons.

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Section: Resultsmentioning

confidence: 99%

Ephrins guide migrating cortical interneurons in the basal telencephalon

Rudolph

Zimmer

Steinecke

et al. 2010

Cell Adhesion & Migration

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“…The fact that a receptor can bind several ligands and vice versa makes this family of molecules a plastic system in which the different affinities and expressions can define an intricate system of possible interactions. Although in many cases it may seem to be redundant, must imply a certain specialization (1,2), and/or the possibility of participating in the regulation of a wide spectrum of cellular functions (3)(4)(5).…”

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confidence: 82%

Thymic Alterations in EphA4-Deficient Mice

Múñoz

Alfaro

García‐Ceca

et al. 2006

The Journal of Immunology

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In the present work, we have demonstrated in vivo an altered maturation of the thymic epithelium that results in defective T cell development which increases with age, in the thymus of Eph A4-deficient mice. The deficient thymi are hypocellular and show decreased proportions of double-positive (CD4+CD8+) cells which reach minimal numbers in 4-wk-old thymi. The EphA4 −/− phenotype correlates with an early block of T cell precursor differentiation that results in accumulation of CD44−CD25+ triple-negative cells and, sometimes, of CD44+CD25− triple-negative thymocytes as well as with increased numbers of apoptotic cells and an important reduction in the numbers of cycling thymocytes. Various approaches support a key role of the thymic epithelial cells in the observed phenotype. Thymic cytoarchitecture undergoes profound changes earlier than those found in the thymocyte maturation. Thymic cortex is extremely reduced and consists of densely packed thymic epithelial cells. Presumably the lack of forward Eph A4 signaling in the Eph A4 −/− epithelial cells affects their development and finally results in altered T cell development.

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“…In the adult, ligand proteins detected by EphA5-AP binding appear as a composite gradient of all three ligands (22). We showed previously that these three ligands have similar activity on hippocampal axons (42,50). In addition, in vitro binding studies suggest these ligands have similar biochemical activity (40).…”

Section: Spatial and Temporal Dynamics Of Ephrin-a Ligand Expressionmentioning

confidence: 99%

Mistargeting hippocampal axons by expression of a truncated Eph receptor

Yue

Chen

Gale

et al. 2002

Proc. Natl. Acad. Sci. U.S.A.

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Topographic mapping of axon terminals is a general principle of neural architecture that underlies the interconnections among many neural structures. The Eph family tyrosine kinase receptors and their ligands, the ephrins, have been implicated in the formation of topographic projection maps. We show that multiple Eph receptors and ligands are expressed in the hippocampus and its major subcortical projection target, the lateral septum, and that expression of a truncated Eph receptor in the mouse brain results in a pronounced alteration of the hippocamposeptal topographic map. Our observations provide strong support for a critical role of Eph family guidance factors in regulating ontogeny of hippocampal projections.I nformation encoding as topographic maps, which reflects the spatial organization of sensory surfaces and body effectors, is a fundamental mechanism of nervous system function (1, 2). Such topographic representation is critically dependent on precise ordering of axon projections, which maintains the spatial organization of neurons in synaptic connections with target neurons. It has been suggested that topographic axon connections allow transfer of spatial information in the sensory systems (3). In the eye, retinal axons form an inverted projection map in the tectum, with dorsal axons projecting to the ventral tectum, and ventral axons to the dorsal tectum. Similarly, retinal ganglion neurons in the temporal and nasal sides send axons to the anterior and posterior regions of the tectum, respectively (4). Comparable mechanisms may also operate in the limbic circuits, where learning, memory, and emotional responses are elaborated. For example, the hippocampus sends axons topographically to the lateral septum, with dorsomedial neurons projecting to the dorsomedial area of the target, and ventrolateral neurons projecting to the ventrolateral septal region (5, 6). Similarity in organizational principles between limbic circuits and sensory systems suggests that learning, memory, and emotions may be governed by the same spatial constraints as sensory information processing.Based on analyses of regenerating retinal axons, Roger Sperry (7) proposed that axons and target neurons carry specific cytochemical identification tags, and that each axon makes synaptic connections only with neurons carrying matching affinity tags. These tags may be distributed as gradients in the projecting and target fields to specify topographic maps. Recent expression and functional studies suggest that ephrins and their receptors serve as the postulated chemoaffinity guidance tags. The ephrins are a family of cell surface molecules that are ligands of the Eph family tyrosine kinase receptors (8). The Eph receptors, EphA3 in the chicken and EphA5͞A6 in the mouse retina, are expressed in a nasal (low) to temporal (high) gradient (3, 9, 10). Complementary to the receptor gradient, the ligands ephrin-A2 and -A5 constitute an anterior (low) to posterior (high) gradient in the optic tectum (9, 11-13). Disruption of the ligand gradient by re...

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Multiple ephrins regulate hippocampal neurite outgrowth

Cited by 26 publications

References 22 publications

Ephrins guide migrating cortical interneurons in the basal telencephalon

Ephrins guide migrating cortical interneurons in the basal telencephalon

Thymic Alterations in EphA4-Deficient Mice

Mistargeting hippocampal axons by expression of a truncated Eph receptor

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