Ephrin‐B3–EphA4 interactions regulate the growth of specific thalamocortical axon populations <i>in vitro</i>

Takemoto, Makoto; Fukuda, Tsuyoshi; Sonoda, Rie; Murakami, Fujio; Tanaka, Hideaki; Yamamoto, Naoya

doi:10.1046/j.1460-9568.2002.02166.x

Cited by 38 publications

(36 citation statements)

References 39 publications

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“…Ephrin-B3 has been noted for its remarkably restricted expression pattern down the midline of the neural tube during development (8,38), suggesting that ephrin-B3 may regulate the midline guidance of axons in forming the spinal cord. In addition, it has also been reported that ephrin-B3 guides regional innervation by suppressing axonal growth of lateral thalamic neurons in developing rat brains (39). Thus, ephrin-B3 is likely to play a critical role in the process of neurodevelopment.…”

Section: Discussionmentioning

confidence: 95%

Ephrin-B3 Ligand Promotes Glioma Invasion through Activation of Rac1

et al. 2006

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Eph receptor tyrosine kinases are involved in nervous system development. Eph ligands, termed ephrins, are transmembrane proteins that bind to Eph receptors, the mutual activation of which causes repulsive effects in reciprocally contacting cells. Previously, we showed that overexpression of EphB2 in glioma cells increases cell invasion. Here, expression profiles of ephrin-B family members were determined in four glioma cell lines and in invading glioblastoma cells collected by laser capture microdissection. Ephrin-B3 mRNA was upregulated in migrating cells of four of four glioma cell lines (1.3-to 1.7-fold) and in invading tumor cells of eight of eight biopsy specimens (1.2-to 10.0-fold). Forced expression of ephrin-B3 in low expressor cell lines (U87, T98G) stimulated cell migration and invasion in vitro and ex vivo, concomitant with tyrosine phosphorylation of ephrin-B3. In high expressor cell lines (U251, SNB19), ephrin-B3 colocalized with Rac1 to lamellipodia of motile wild-type cells. Cells transfected with ephrin-B3 small interfering RNA (siRNA) showed significant morphologic change and decreased invasion in vitro and ex vivo. Depletion of endogenous ephrin-B3 expression abrogated the increase of migration and invasion induced by EphB2/Fc, indicating increased invasion is dependent on ephrin-B3 activation. Furthermore, using a Rac1-GTP pulldown assay, we showed that ephrin-B3 is associated with Rac1 activation. Reduction of Rac1 by siRNA negated the increased invasion by addition of EphB2/Fc. In human glioma specimens, ephrin-B3 expression and phosphorylation correlated with increasing tumor grade. Immunohistochemistry revealed robust staining for phosphorylated ephrin-B and ephrin-B3 in invading glioblastoma cells. These data show that ephrin-B3 expression and signaling through Rac1 are critically important to glioma invasion. (Cancer Res 2006; 66(17): 8492-500)

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Section: Discussionmentioning

confidence: 95%

Ephrin-B3 Ligand Promotes Glioma Invasion through Activation of Rac1

et al. 2006

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“…distributed (Suzuki et al, 1997;Inoue et al, 1998;Mackarehtschian et al, 1999;Miyashita-Lin et al, 1999;Nakagawa et al, 1999;Yun et al, 2003) and associated with thalamocortical axon growth and guidance (Gao et al, 1998;Takemoto et al, 2002). Ephrin-A5 is one example of a likely mediator of FGF8/17 signaling.…”

Section: Discussionmentioning

confidence: 99%

Fibroblast Growth Factor 8 Regulates Neocortical Guidance of Area-Specific Thalamic Innervation

Shimogori¹,

Grove²

2005

J. Neurosci.

100

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Thalamic innervation of each neocortical area is vital to cortical function, but the developmental strategies that guide axons to specific areas remain unclear. We took a new approach to determine the contribution of intracortical cues. The cortical patterning molecule fibroblast growth factor 8 (FGF8) was misexpressed in the cortical primordium to rearrange the area map. Thalamic axons faithfully tracked changes in area position and innervated duplicated somatosensory barrel fields induced by an ectopic source of FGF8, indicating that thalamic axons indeed use intracortical positional information. Because cortical layers are generated in temporal order, FGF8 misexpression at different ages could be used to shift regional identity in the subplate and cortical plate either in or out of register. Thalamic axons showed strikingly different responses in the two different conditions, disclosing sources of positional guidance in both subplate and cortical plate. Unexpectedly, axon trajectories indicated that an individual neocortical layer could provide not only laminar but also area-specific guidance. Our findings demonstrate that thalamocortical axons are directed by sequential, positional cues within the cortex and implicate FGF8 as an indirect regulator of thalamocortical innervation.

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“…In situ hybridization was performed as described (Takemoto et al, 2002;Okabe et al, 2004a) with some modifications. In brief, mRNA probes were labeled with digoxigenin-UTP by RNA in vitro transcription according to the manufacturer's protocol (Roche Diagnostics).…”

Section: In Situ Hybridizationmentioning

confidence: 99%

Roles of cell-adhesion molecules nectin 1 and nectin 3 in ciliary body development

et al. 2005

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Nectins are Ca2+-independent immunoglobulin-like cell-cell-adhesion molecules consisting of four members. Nectins homophilically and heterophilically trans-interact to form a variety of cell-cell junctions, including cadherin-based adherens junctions in epithelial cells and fibroblasts in culture, synaptic junctions in neurons, and Sertoli cell-spermatid junctions in the testis, in cooperation with, or independently of, cadherins. To further explore the function of nectins, we generated nectin 1–/– and nectin 3–/– mice. Both nectin 1–/– and nectin 3–/– mice showed a virtually identical ocular phenotype, microphthalmia, accompanied by a separation of the apex-apex contact between the pigment and non-pigment cell layers of the ciliary epithelia. Immunofluorescence and immunoelectron microscopy revealed that nectin 1 and nectin 3, but not nectin 2, localized at the apex-apex junctions between the pigment and non-pigment cell layers of the ciliary epithelia. However, nectin 1–/– and nectin 3–/– mice showed no impairment of the apicolateral junctions between the pigment epithelia where nectin 1, nectin 2 and nectin 3 localized, or of the apicolateral junctions between the non-pigment epithelia where nectin 2 and nectin 3, but not nectin 1, localized. These results indicate that the heterophilic trans-interaction between nectin 1 and nectin 3 plays a sentinel role in establishing the apex-apex adhesion between the pigment and non-pigment cell layers of the ciliary epithelia that is essential for the morphogenesis of the ciliary body.

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Ephrin‐B3–EphA4 interactions regulate the growth of specific thalamocortical axon populations in vitro

Cited by 38 publications

References 39 publications

Ephrin-B3 Ligand Promotes Glioma Invasion through Activation of Rac1

Ephrin-B3 Ligand Promotes Glioma Invasion through Activation of Rac1

Fibroblast Growth Factor 8 Regulates Neocortical Guidance of Area-Specific Thalamic Innervation

Roles of cell-adhesion molecules nectin 1 and nectin 3 in ciliary body development

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