Graded and Lamina-Specific Distributions of Ligands of EphB Receptor Tyrosine Kinases in the Developing Retinotectal System

Braisted, Janet E.; McLaughlin, Todd; Wang, Hai U.; Friedman, Glenn C.; Anderson, David J.; O’Leary, Dennis D.M.

doi:10.1006/dbio.1997.8706

Cited by 142 publications

(108 citation statements)

References 50 publications

Supporting

Mentioning

100

Contrasting

Order By: Relevance

“…This finding suggested that ligands that stimulate EphB2 phosphorylation must also be expressed in this tissue. Indeed, ephrin-B1 and ephrin-B2 are expressed in the embryonic retina (20,24). Consistent with binding of ephrin-B1 to EphB2 in the retina, we show here that not only EphB2 but also ephrin-B1 is phosphorylated on tyrosine in retinal tissue.…”

Section: Discussionsupporting

confidence: 88%

“…onic retina is intriguing because these proteins have complementary patterns of expression; ephrin-B1 is most highly expressed in the dorsal retina, and EphB2 is most highly expressed in the ventral retina (Fig. 5, A and B) (20,24,25). However, we found that ephrin-B1 is also expressed at low levels in the ventral retina and that EphB2 is also expressed in the dorsal retina (Fig.…”

Section: Ephrin-b1 and Ephb2 In Vivo Tyrosine Phosphorylation Sitesmentioning

confidence: 66%

“…Indeed ephrin-B1 and ephrin-B2, two ligands for EphB2, are expressed in the embryonic neural retina (Fig. 4A) (20,24). According to the reverse signaling model, ephrin-B ligands in the retina should be phosphorylated on tyrosine upon interaction with EphB2.…”

Section: Ephrin-b1 and Ephb2 In Vivo Tyrosine Phosphorylation Sitesmentioning

confidence: 99%

See 2 more Smart Citations

In Vivo Tyrosine Phosphorylation Sites of Activated Ephrin-B1 and EphB2 from Neural Tissue

Kalo

Pasquale

2001

Journal of Biological Chemistry

View full text Add to dashboard Cite

EphB2 is a receptor tyrosine kinase of the Eph family and ephrin-B1 is one of its transmembrane ligands. In the embryo, EphB2 and ephrin-B1 participate in neuronal axon guidance, neural crest cell migration, the formation of blood vessels, and the development of facial structures and the inner ear. Interestingly, EphB2 and ephrin-B1 can both signal through their cytoplasmic domains and become tyrosine-phosphorylated when bound to each other. Tyrosine phosphorylation regulates EphB2 signaling and likely also ephrin-B1 signaling. Embryonic retina is a tissue that highly expresses both ephrin-B1 and EphB2. Although the expression patterns of EphB2 and ephrin-B1 in the retina are different, they partially overlap, and both proteins are substantially tyrosine-phosphorylated. To understand the role of ephrin-B1 phosphorylation, we have identified three tyrosines of ephrin-B1 as in vivo phosphorylation sites in transfected 293 cells stimulated with soluble EphB2 by using mass spectrometry and site-directed mutagenesis. These tyrosines are also physiologically phosphorylated in the embryonic retina, although the extent of phosphorylation at each site may differ.

show abstract

Section: Discussionsupporting

confidence: 88%

Section: Ephrin-b1 and Ephb2 In Vivo Tyrosine Phosphorylation Sitesmentioning

confidence: 66%

See 1 more Smart Citation

In Vivo Tyrosine Phosphorylation Sites of Activated Ephrin-B1 and EphB2 from Neural Tissue

Kalo

Pasquale

2001

Journal of Biological Chemistry

View full text Add to dashboard Cite

show abstract

“…Exactly the same number of genes was found to be enriched in the dorsal retina, using the same criteria (SI Table 10). Five of the 10 most highly enriched ''dorsal'' genes were genes previously shown to be enriched in the dorsal retina: Tbx5, Ephrin B2 (Efnb2), COUP-TFII (Nr2f2), Raldh1 (Aldh1a1), and Cyb1b1 (13)(14)(15)(16)(17)(18). In addition, the two dorsal Ͼ ventral cone genes discussed above, Opn1mw (M-opsin), Smug1, and one additional cone gene, Arr3, were also found to be among the top 21 most dorsally enriched genes.…”

Section: Dorsal-ventral (D-v) Patterning Of Photoreceptor Genes Suggementioning

confidence: 99%

A typology of photoreceptor gene expression patterns in the mouse

Corbo

Myers

Lawrence

et al. 2007

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

View full text Add to dashboard Cite

Mutations in photoreceptor-enriched genes have been implicated in dozens of human retinal diseases, yet no systematic analysis of rod and cone gene expression patterns has been carried out. In addition, although cone photoreceptor loss accounts for much of the morbidity of retinal disease, relatively few cone-specific genes are known. In this study, we carried out microarray and in situ hybridization analyses of the mouse Neural retina leucine zipper gene (Nrl) mutant, which shows an en masse conversion of rods into cones, to establish a typology of photoreceptor gene expression and to identify novel cone-specific genes. We found a total of 18 new cone-enriched genes, some of which map near uncloned retinal disease loci. Several of these genes have a dorsal-ventral (D-V) pattern of expression similar to that of short-or mediumwavelength opsins. We carried out microarray analysis of dorsal and ventral microdissected WT retina and found additional photoreceptor genes with an asymmetric distribution. Overall, we found that photoreceptor genes fall on an expression spectrum from rod-specific to cone-specific, with many showing varying degrees of rod and cone coexpression. These expression patterns can be reliably predicted from microarray data alone. Our results demonstrate definitive molecular differences between rods and cones that may underlie the physiological differences between these two classes of photoreceptors.blindness ͉ cone photoreceptor ͉ retina ͉ rod photoreceptor

show abstract

“…After CALI of ephrin-A5, tecta were dissected and incubated with 0.3 nM EphA3-AP for 30 min (24). After rinsing, tecta were fixed with 4% paraformaldehyde, and endogenous AP activity was heat inactivated at 65°C for 45 min.…”

Section: Animalsmentioning

confidence: 99%

Ephrin-A5 restricts topographically specific arborization in the chick retinotectal projection in vivo

Sakurai

Wong

Drescher

et al. 2002

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

View full text Add to dashboard Cite

The retinotectal map is the best characterized model system to study how axons respond to guidance cues during the formation of the nervous system. Recent studies have shown that the critical event in forming this map is topographic-specific axon branching. To elucidate the in vivo role of the repulsive cue ephrin-A5 in this event, we used chromophore-assisted laser inactivation (CALI) to generate acute loss of ephrin-A5 function in localized areas of the posterior tectum of chick embryos in ovo and analyzed the resulting changes of retinal projections during initial outgrowth (E11) and when retinal axons arborize in the deep layers in the tectum (E12). We confirmed that ephrin-A5 functions to restrict initial axon outgrowth at E11. At E12, CALI of ephrin-A5 did not affect the extent of axon outgrowth on the tectal surface but instead caused ectopic arborization posterior to the topographically correct site in deeper layers of the tectum. This shows that ephrin-A5 restricts arborization during this critical process for developing the retinotopic map. CALI provides an approach to inactivate in vivo function in higher vertebrates with high temporal and spatial specificity that may have wide application.T he retinotectal projection is a well established model system to study mechanisms that form the topographic map of neural connections in the brain. It is thought that molecules expressed in gradients guide axons to their precise topographic targets. This chemoaffinity hypothesis proposed by Sperry (1) has been supported by the identification of molecular cues expressed in gradients in the retina and in the tectum (2). One important guidance cue is ephrin-A5 (3). The graded expression of ephrin-A ligands in the tectum coupled with expression of the Eph receptors that bind these ligands in retinal axons provides a potential molecular mechanism for defining the anteriorposterior (A-P) map (3, 4). Ephrin-A5 (5) is predominantly expressed in the posterior half of the chick tectum in a steep gradient, whereas a second ephrin, ephrin-A2 (6), is expressed in a shallower gradient across the entire tectum (7), and both gradients exist throughout the formation of the retinotectal map. These expression patterns suggest that ephrin-A5 and ephrin-A2 act in the graded repulsion of retinal axons involved in mapping. This notion is supported by aberrant retinal axon extension beyond their target areas observed in embryos with single and double deletions of the ephrin-A5 and ephrin-A2 genes (8, 9). These genetic deletion studies showed the overall importance of ephrin-A ligands as topographic labels, but how these ligands act in vivo has not been demonstrated.In mammals and avians, the development of topographical order occurs through a multistep process: initial axon outgrowth, topographically specific arborization, and remodeling (10, 11). Initial axon outgrowth is relatively inaccurate, and axons often overshoot beyond their correct termination zone (TZ). Topographically specific branching and arborization in higher vertebrates ...

show abstract

Graded and Lamina-Specific Distributions of Ligands of EphB Receptor Tyrosine Kinases in the Developing Retinotectal System

Cited by 142 publications

References 50 publications

In Vivo Tyrosine Phosphorylation Sites of Activated Ephrin-B1 and EphB2 from Neural Tissue

In Vivo Tyrosine Phosphorylation Sites of Activated Ephrin-B1 and EphB2 from Neural Tissue

A typology of photoreceptor gene expression patterns in the mouse

Ephrin-A5 restricts topographically specific arborization in the chick retinotectal projection in vivo

Contact Info

Product

Resources

About