Genetic analysis of the role of Eph receptors in the development of the mammalian nervous system

Frisén, Jonas; Barbacid, Mariano

doi:10.1007/s004410050925

Cited by 17 publications

(8 citation statements)

References 43 publications

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“…(36) There is also an increasing body of evidence that suggests a role for Eph family molecules in regulating axon growth at the midline of the central nervous system. For example, genetic analysis of mice lacking Eph receptors revealed defects in the formation of commissures in the forebrain, (37,38) guidance of contralaterally projecting tectal axons, (39) and decussation of the corticospinal tract. (40) Recent investigations that examined the molecular nature of axon guidance at the optic chiasm in rodents have involved ephrin-A ligands.…”

Section: The Role Of Eph Family Molecules In Guiding Ipsilateral Retimentioning

confidence: 99%

Control of retinal growth and axon divergence at the chiasm: lessons from Xenopus

Mann

Holt

2001

BioEssays

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Metamorphosis in frogs is a critical developmental process through which a tadpole changes into an adult froglet. Metamorphic changes include external morphological transformations as well as important changes in the wiring of sensory organs and central nervous system. This review aims to provide an overview on the events that occur in the visual system of metamorphosing amphibians and to discuss recent studies that provide new insight into the molecular mechanisms that control changes in the retinal growth pattern as well as the formation of new axonal pathways in the central nervous system. BioEssays 23:319-326, 2001.

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Section: The Role Of Eph Family Molecules In Guiding Ipsilateral Retimentioning

confidence: 99%

Control of retinal growth and axon divergence at the chiasm: lessons from Xenopus

Mann

Holt

2001

BioEssays

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“…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)(12)(13). Disruption of the ligand gradient by retrovirus-mediated gene expression or by gene manipulation techniques resulted in mistargeting of retinal axons (3,(14)(15)(16)(17)(18)(19). These analyses suggest critical roles of ephrins and their receptors in regulating development of retinotectal topographic map.…”

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confidence: 92%

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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“…Eph receptor and ephrin signaling has been shown to play a prominent role during embryogenesis, but a growing body of evidence indicates that adult epithelial tissues are another major site for Eph receptor and ephrin ligand action. [9][10][11][12][13][14] Epithelial tissues line body surfaces and cavities. They are composed of single (simple) or multiple (stratified) layers of epithelial cells that are tightly anchored to the underlying basement membrane and one another via specialized junctional complexes; these include integrin-based adhesion complexes for cell-extracellular matrix anchorage points while adherens junctions, desmosomes, tight junctions, and gap junctions are found at cell-cell contacts.…”

Section: Introductionmentioning

confidence: 99%

Eph receptor and ephrin function in breast, gut, and skin epithelia

White¹,

Getsios

2014

Cell Adhesion & Migration

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Abbreviations: ADAM, a disintegrin and metalloprotease; Apc, adenomatous polyposis coli; Eph, erythropoietin-producing hepatocellular; ER, estrogen receptor; Erk, extracellular signal-regulated kinase; GEF, guanine nucleotide exchange factor; GPI, glycosylphosphatidylinositol; HER2, human epidermal growth factor receptor 2; HGF, hepatocyte growth factor; IBD, inflammatory bowel disease; KLF, Kr€ uppel-like factor; MAPK, mitogen-activated protein kinase; MMTV-LTR, mouse mammary tumor virus-long terminal repeat; MT1-MMP, membrane-type 1 matrix metalloproteinase; PDZ, postsynaptic density protein 95, discs large 1, and zonula occludens-1; PTP, protein tyrosine phosphatase; RTK, receptor tyrosine kinase; SH2, Src homology 2; SHIP2, SH2 inositol phosphatase 2; SLAP, Src-like adaptor protein; TCF, T-cell specific transcription factor; TEB, terminal end bud; TNFa, tumor necrosis factor a:Epithelial cells are tightly coupled together through specialized intercellular junctions, including adherens junctions, desmosomes, tight junctions, and gap junctions. A growing body of evidence suggests epithelial cells also directly exchange information at cell-cell contacts via the Eph family of receptor tyrosine kinases and their membrane-associated ephrin ligands. Ligand-dependent and -independent signaling via Eph receptors as well as reverse signaling through ephrins impact epithelial tissue homeostasis by organizing stem cell compartments and regulating cell proliferation, migration, adhesion, differentiation, and survival. This review focuses on breast, gut, and skin epithelia as representative examples for how Eph receptors and ephrins modulate diverse epithelial cell responses in a context-dependent manner. Abnormal Eph receptor and ephrin signaling is implicated in a variety of epithelial diseases raising the intriguing possibility that this cellcell communication pathway can be therapeutically harnessed to normalize epithelial function in pathological settings like cancer or chronic inflammation.

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Genetic analysis of the role of Eph receptors in the development of the mammalian nervous system

Cited by 17 publications

References 43 publications

Control of retinal growth and axon divergence at the chiasm: lessons from Xenopus

Control of retinal growth and axon divergence at the chiasm: lessons from Xenopus

Mistargeting hippocampal axons by expression of a truncated Eph receptor

Eph receptor and ephrin function in breast, gut, and skin epithelia

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