Regulation of repulsion versus adhesion by different splice forms of an Eph receptor

Holmberg, Johan; Clarke, Diana L.; Frisén, Jonas

doi:10.1038/35041577

Cited by 320 publications

(290 citation statements)

References 28 publications

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“…An earlier study also showed that purified ephrin-A1 stimulated neurite outgrowth of spinal motor neurons (45). In addition, a truncated form of EphA7 mediates attractive interaction with ephrin-A5 in neural tube closure during development (47). The ventroward shift may reflect attractive interactions between EphA5(KϪ) transgene protein with the ligands in the septal target, in the absence of repulsive interactions caused by the inhibition of endogenous EphA receptors.…”

Section: Expression Of a Truncated Epha Receptor Alters Hippocampal Axonmentioning

confidence: 95%

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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Section: Expression Of a Truncated Epha Receptor Alters Hippocampal Axonmentioning

confidence: 95%

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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“…Binding of clustered ephrin-A ligands to the full-length EphA7 receptor results in phosphorylation of its intracellular kinase domain, initiating a signaling cascade that results in cell repulsion (Holmberg et al, 2000). This prompted us to ask whether soluble EphA7 can affect ephrinA ligand-induced activation of full-length Eph receptor.…”

Section: Soluble Epha7 Blocks Ephrin-a4-mediated Activation Of Full-lmentioning

confidence: 99%

Global DNA methylation profiling reveals silencing of a secreted form of Epha7 in mouse and human germinal center B-cell lymphomas

et al. 2007

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Most human lymphomas originate from transformed germinal center (GC) B lymphocytes. While activating mutations and translocations of MYC, BCL2 and BCL6 promote specific GC lymphoma subtypes, other genetic and epigenetic modifications that contribute to malignant progression in the GC remain poorly defined. Recently, aberrant expression of the TCL1 proto-oncogene was identified in major GC lymphoma subtypes. TCL1 transgenic mice offer unique models of both aggressive GC and marginal zone B-cell lymphomas, further supporting a role for TCL1 in B-cell transformation. Here, restriction landmark genomic scanning was employed to discover tumor-associated epigenetic alterations in malignant GC and marginal zone B-cells in TCL1 transgenic mice. Multiple genes were identified that underwent DNA hypermethylation and decreased expression in TCL1 transgenic tumors. Further, we identified a secreted isoform of EPHA7, a member of the Eph family of receptor tyrosine kinases that are able to influence tumor invasiveness, metastasis and neovascularization. EPHA7 was hypermethylated and repressed in both mouse and human GC B-cell non-Hodgkin lymphomas, with the potential to influence tumor progression and spread. These data provide the first set of hypermethylated genes with the potential to complement TCL1-mediated GC B-cell transformation and spread.

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“…The individual function of EphA7 was assessed in the developing GT vasculature using a null EphA7 allele (Holmberg et al, 2000). A comparison of the GT vessel diameters between wild-type and EphA7 homozygous mutant embryos revealed no significant expansions of the GT vessels (Fig.…”

Section: Loss Of Epha7 Is Not Sufficient To Cause Gross Enlargement Omentioning

confidence: 99%

HOXA13 directly regulates EphA6 and EphA7 expression in the genital tubercle vascular endothelia

Shaut¹,

Saneyoshi²,

Morgan³

et al. 2007

Developmental Dynamics

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Hypospadias, a common defect affecting the growth and closure of the external genitalia, is often accompanied by gross enlargements of the genital tubercle (GT) vasculature. Because Hoxa13 homozygous mutant mice also exhibit hypospadias and GT vessel expansion, we examined whether genes playing a role in angiogenesis exhibit reduced expression in the GT. From this analysis, reductions in EphA6 and EphA7 were detected. Characterization of EphA6 and EphA7 expression in the GT confirmed colocalization with HOXA13 in the GT vascular endothelia. Analysis of the EphA6 and EphA7 promoter regions revealed a series of highly conserved cis-regulatory elements bound by HOXA13 with high affinity. GT chromatin immunoprecipitation confirmed that HOXA13 binds these gene-regulatory elements in vivo. In vitro, HOXA13 activates gene expression through the EphA6 and EphA7 gene-regulatory elements. Together these findings indicate that HOXA13 directly regulates EphA6 and EphA7 in the developing GT and identifies the GT vascular endothelia as a novel site for HOXA13-dependent expression of EphA6 and EphA7. Developmental Dynamics 236:951-960, 2007.

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Regulation of repulsion versus adhesion by different splice forms of an Eph receptor

Cited by 320 publications

References 28 publications

Mistargeting hippocampal axons by expression of a truncated Eph receptor

Mistargeting hippocampal axons by expression of a truncated Eph receptor

Global DNA methylation profiling reveals silencing of a secreted form of Epha7 in mouse and human germinal center B-cell lymphomas

HOXA13 directly regulates EphA6 and EphA7 expression in the genital tubercle vascular endothelia

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