QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

HOME  |   SEARCH  |   ARCHIVE  |   SUBSCRIBE  |   CONTACT  |   HELP

The Journal of Neuroscience, March 10, 2004, 24(10):2542-2550; doi:10.1523/JNEUROSCI.0239-03.2004

This Article Full Text Full Text (PDF) Submit an eLetter Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Web of Science (47) Citing Articles via Google Scholar Google Scholar Articles by Feldheim, D. A. Articles by Flanagan, J. G. Search for Related Content PubMed PubMed Citation Articles by Feldheim, D. A. Articles by Flanagan, J. G. Pubmed/NCBI databases Gene GEO Profiles HomoloGene Protein UniGene

 Previous Article  |  Next Article 

Development/Plasticity/Repair
Loss-of-Function Analysis of EphA Receptors in Retinotectal Mapping

David A. Feldheim,^1 * Masaru Nakamoto,^1 * Miriam Osterfield,¹ Nicholas W. Gale,² Thomas M. DeChiara,² Rajat Rohatgi,¹ George D. Yancopoulos,² and John G. Flanagan¹

¹Department of Cell Biology and Program in Neuroscience, Harvard Medical School, Boston, Massachusetts 02115, and ²Regeneron Pharmaceuticals, Inc., Tarrytown, New York 10591

EphA tyrosine kinases are thought to act as topographically specific receptors in the well-characterized projection map from the retina to the tectum. Here, we describe a loss-of-function analysis of EphA receptors in retinotectal mapping. Expressing patches of a cytoplasmically truncated EphA3 receptor in chick retina caused temporal axons to have reduced responsiveness to posterior tectal repellent activity in vitro and to shift more posteriorly within the map in vivo. A gene disruption of mouse EphA5, replacing the intracellular domain with -galactosidase, reduced in vitro responsiveness of temporal axons to posterior target membranes. It also caused map abnormalities in vivo, with temporal axons shifted posteriorly and nasal axons anteriorly, but with the entire target still filled by retinal axons. The anterior shift of nasal axons was not accompanied by increased responsiveness to tectal repellent activity, in contrast to the comparable anterior shift in ephrin-A knock-outs, helping to resolve a previous ambiguity in interpreting the ephrin gene knock-outs. The results show the functional requirement for endogenous EphA receptors in retinotectal mapping, show that the receptor intracellular domain is required for a forward signaling response to topographic cues, and provide new evidence for a role of axon competition in topographic mapping.

Key words: Eph; ephrin; retina; axon; topographic; receptor

---

Received Jan 27, 2003; revised November 24, 2003; accepted December 30, 2003.

This article has been cited by other articles:

				J. Cang, L. Wang, M. P. Stryker, and D. A. Feldheim Roles of Ephrin-As and Structured Activity in the Development of Functional Maps in the Superior Colliculus J. Neurosci., October 22, 2008; 28(43): 11015 - 11023. [Abstract] [Full Text] [PDF]

				W. Chen, V. Kalscheuer, A. Tzschach, C. Menzel, R. Ullmann, M. H. Schulz, F. Erdogan, N. Li, Z. Kijas, G. Arkesteijn, et al. Mapping translocation breakpoints by next-generation sequencing Genome Res., July 1, 2008; 18(7): 1143 - 1149. [Abstract] [Full Text] [PDF]

				M. Buhusi, M. C. Schlatter, G. P. Demyanenko, R. Thresher, and P. F. Maness L1 Interaction with Ankyrin Regulates Mediolateral Topography in the Retinocollicular Projection J. Neurosci., January 2, 2008; 28(1): 177 - 188. [Abstract] [Full Text] [PDF]

				C. Pfeiffenberger, J. Yamada, and D. A. Feldheim Ephrin-As and Patterned Retinal Activity Act Together in the Development of Topographic Maps in the Primary Visual System J. Neurosci., December 13, 2006; 26(50): 12873 - 12884. [Abstract] [Full Text] [PDF]

				A. Dufour, J. Egea, K. Kullander, R. Klein, and P. Vanderhaeghen Genetic analysis of EphA-dependent signaling mechanisms controlling topographic mapping in vivo Development, November 15, 2006; 133(22): 4415 - 4420. [Abstract] [Full Text] [PDF]

				H. Sakuta, H. Takahashi, T. Shintani, K. Etani, A. Aoshima, and M. Noda Role of bone morphogenic protein 2 in retinal patterning and retinotectal projection. J. Neurosci., October 18, 2006; 26(42): 10868 - 10878. [Abstract] [Full Text] [PDF]

				Y. Zhu, S. Guthrie, and F. Murakami Ephrin A/EphA controls the rostral turning polarity of a lateral commissural tract in chick hindbrain. Development, October 1, 2006; 133(19): 3837 - 3846. [Abstract] [Full Text] [PDF]

				B. K Mueller, T. Yamashita, G. Schaffar, and R. Mueller The role of repulsive guidance molecules in the embryonic and adult vertebrate central nervous system Phil Trans R Soc B, September 29, 2006; 361(1473): 1513 - 1529. [Abstract] [Full Text] [PDF]

				A. C. von Philipsborn, S. Lang, J. Loeschinger, A. Bernard, C. David, D. Lehnert, F. Bonhoeffer, and M. Bastmeyer Growth cone navigation in substrate-bound ephrin gradients Development, July 1, 2006; 133(13): 2487 - 2495. [Abstract] [Full Text] [PDF]

				M.-A. Lambot, F. Depasse, J.-C. Noel, and P. Vanderhaeghen Mapping Labels in the Human Developing Visual System and the Evolution of Binocular Vision J. Neurosci., August 3, 2005; 25(31): 7232 - 7237. [Abstract] [Full Text] [PDF]

				A. R. Chandrasekaran, D. T. Plas, E. Gonzalez, and M. C. Crair Evidence for an Instructive Role of Retinal Activity in Retinotopic Map Refinement in the Superior Colliculus of the Mouse J. Neurosci., July 20, 2005; 25(29): 6929 - 6938. [Abstract] [Full Text] [PDF]

				J. A. Gamble, D. K. Karunadasa, J.-R. Pape, M. J. Skynner, M. G. Todman, R. J. Bicknell, J. P. Allen, and A. E. Herbison Disruption of Ephrin Signaling Associates with Disordered Axophilic Migration of the Gonadotropin-Releasing Hormone Neurons J. Neurosci., March 23, 2005; 25(12): 3142 - 3150. [Abstract] [Full Text] [PDF]

Home  |   Search  |   Archive  |   Subscribe  |   Contact  |   Help