Topographic Targeting and Pathfinding Errors of Retinal Axons Following Overexpression of EphrinA Ligands on Retinal Ganglion Cell Axons

Dütting, Dieter; Handwerker, Claudia; Drescher, Uwe

doi:10.1006/dbio.1999.9489

Cited by 68 publications

(35 citation statements)

References 55 publications

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“…Novel experimental results by Hornberger et al (1999) and Du« tting et al (1999), however, indicate an additional function of the guidance ligands. These showed that the ligands are expressed not only on the tectum, but also on retinal ganglion cells.…”

Section: Models Based On the Imprint-matching Concept Of Retinotectalmentioning

confidence: 95%

Reading of concentration gradients by axonal growth cones

Löschinger

Weth

Bonhoeffer

2000

Phil. Trans. R. Soc. Lond. B

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Wiring up the nervous system occurs as a self-organizing process during animal development. It has long been proposed that directional growth of axons towards their targets is achieved by gradients of guiding molecules and the conceptual framework of gradient guidance was introduced more than a decade ago. Novel experimental results now allow the formulation of models incorporating more mechanistic detail. We ¢rst summarize some crucial in vitro and in vivo results concerning the development of the chick retinotectal projection. We then review two recent theoretical models based on these ¢ndings (the models of Nakamoto and colleagues, and of Honda). Neither model considers the latest observation that putative guidance ligands, in addition to their tectal expression, are expressed in a similar pattern on the retina and that a disturbance of this expression a¡ects topography. These ¢ndings suggest that retinal axons might grow into the tectum until they have reached a ligand concentration matching that of their site of origin. We call this the imprint-matching concept of retinotectal guidance. As a framework for pinpointing logical di¤culties of the mechanistic description of the guidance process and to stimulate further experiments we ¢nally suggest two extended versions of Honda's model implementing imprint matching, which we call`the variable set-point' and`the gradient-sensitive adaptation' model. Strengths and weaknesses of both mechanisms are discussed.

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Section: Models Based On the Imprint-matching Concept Of Retinotectalmentioning

confidence: 95%

Reading of concentration gradients by axonal growth cones

Löschinger

Weth

Bonhoeffer

2000

Phil. Trans. R. Soc. Lond. B

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“…The ligands of EphA receptors, ephrin-A2 and ephrin-A5, have been reported to be expressed in the nasal retina and control the retinotectal projection along the A-P axis by modulating EphA receptor function (Dütting et al, 1999;Hornberger et al, 1999). Ephrin-A2, but not ephrin-A5, was found to be expressed with a V/N-high oblique-gradient at E8 (Fig.…”

Section: Oblique-gradient Molecules In the Retinamentioning

confidence: 99%

Role of Bone Morphogenic Protein 2 in Retinal Patterning and Retinotectal Projection

Sakuta¹,

Takahashi²,

Shintani³

et al. 2006

J. Neurosci.

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It has been long believed that the anteroposterior (A-P) and dorsoventral (D-V) axes in the developing retina are determined independently and also that the retinotectal projection along the two axes is controlled independently. However, we recently demonstrated that misexpression of Ventroptin, a bone morphogenic protein (BMP) antagonist, in the developing chick retina alters the retinotectal projection not only along the D-V (or mediolateral) axis but also along the A-P axis. Moreover, the dorsal-high expression of BMP4 is relieved by the dorsotemporal-high expression of BMP2 at embryonic day 5 (E5) in the retina, during which Ventroptin continuously counteracts the two BMPs keeping on the countergradient expression pattern, respectively. Here, we show that the topographic molecules so far reported to have a gradient only along the D-V axis and ephrin-A2 so far only along the A-P axis are both controlled by the BMP signal, and that they are expressed in a gradient manner along the tilted axis from E6 on in the developing chick retina: the expression patterns of these oblique-gradient molecules are all changed, when BMP2 expression is manipulated in the developing retina. Furthermore, in both BMP2 knockdown embryos and ephrin-A2-misexpressed embryos, the retinotectal projection is altered along the two orthogonal axes. The expressional switching from BMP4 to BMP2 thus appears to play a key role in the retinal patterning and topographic retinotectal projection by tilting the D-V axis toward the posterior side during retinal development. Our results also indicate that BMP2 expression is essential for the maintenance of regional specificity along the revised D-V axis.

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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: 91%

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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Topographic Targeting and Pathfinding Errors of Retinal Axons Following Overexpression of EphrinA Ligands on Retinal Ganglion Cell Axons

Cited by 68 publications

References 55 publications

Reading of concentration gradients by axonal growth cones

Reading of concentration gradients by axonal growth cones

Role of Bone Morphogenic Protein 2 in Retinal Patterning and Retinotectal Projection

Mistargeting hippocampal axons by expression of a truncated Eph receptor

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