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

HOME  |   SEARCH  |   ARCHIVE  |   SUBSCRIBE  |   CONTACT  |   HELP

The Journal of Neuroscience, April 14, 2004, 24(15):3862-3869; doi:10.1523/JNEUROSCI.5296-03.2004

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 ISI 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 ISI Web of Science (33) Citing Articles via Google Scholar Google Scholar Articles by Brinks, H. Articles by Skutella, T. Search for Related Content PubMed PubMed Citation Articles by Brinks, H. Articles by Skutella, T.

 Previous Article  |  Next Article 

Development/Plasticity/Repair
The Repulsive Guidance Molecule RGMa Is Involved in the Formation of Afferent Connections in the Dentate Gyrus

Henriette Brinks,^1,2 * Sabine Conrad,^4 * Johannes Vogt,^2 * Judit Oldekamp,^3 * Ana Sierra,^5 * Lutz Deitinghoff,⁷ Ingo Bechmann,² Gonzalo Alvarez-Bolado,³  Bernd Heimrich,^2,8  Philippe P. Monnier,⁶  Bernhard K. Mueller,⁷  and Thomas Skutella^1,4

¹Neuroscience Research Center and ²Center for Anatomy, Institute of Cell Biology and Neurobiology, Charité Central Campus, 10098 Berlin, Germany, ³Max-Planck-Institute of Experimental Endocrinology, 30625 Hannover, Germany, ⁴Institute of Anatomy, Department of Experimental Embryology, Tissue Engineering Division, and ⁵Department of Ophthalmology, University of Tübingen, 72074 Tübingen, Germany, ⁶Toronto Western Research Institute, Toronto, Ontario, N5T 258 Canada, ⁷CNS Research, Abbott GmbH and Company KG, 67061 Ludwigshafen, Germany, and ⁸Institute of Anatomy and Cell Biology, University of Freiburg, 79104 Freiburg, Germany

In the developing dentate gyrus, afferent fiber projections terminate in distinct laminas. This relies on an accurately regulated spatiotemporal network of guidance molecules. Here, we have analyzed the functional role of the glycosylphosphatidylinositol (GPI)-anchored repulsive guidance molecule RGMa. In situ hybridization in embryonic and postnatal brain showed expression of RGMa in the cornu ammonis and hilus of the hippocampus. In the dentate gyrus, RGM immunostaining was confined to the inner molecular layer, whereas the outer molecular layers targeted by entorhinal fibers remained free. To test the repulsive capacity of RGMa, different setups were used: the stripe and explant outgrowth assays with recombinant RGMa, and entorhino–hippocampal cocultures incubated either with a neutralizing RGMa antibody (Ab) or with the GPI anchor-digesting drug phosphatidylinositol-specific phospholipase C. Entorhinal axons were clearly repelled by RGMa in the stripe and outgrowth assays. After disrupting the RGMa function, the specific laminar termination pattern in entorhino–hippocampal cocultures was lost, and entorhinal axons entered inappropriate hippocampal areas. Our data indicate an important role of RGMa for the layer-specific termination of the perforant pathway as a repulsive signal that compels entorhinal fibers to stay in their correct target zone.

Key words: axon; dentate; development; guidance; hippocampus; neuron

---

Received Dec 1, 2003; revised February 17, 2004; accepted February 18, 2004.

This article has been cited by other articles:

				D. De Pietri Tonelli, J. N. Pulvers, C. Haffner, E. P. Murchison, G. J. Hannon, and W. B. Huttner miRNAs are essential for survival and differentiation of newborn neurons but not for expansion of neural progenitors during early neurogenesis in the mouse embryonic neocortex Development, December 1, 2008; 135(23): 3911 - 3921. [Abstract] [Full Text] [PDF]

				Y. Ohshima, T. Kubo, R. Koyama, M. Ueno, M. Nakagawa, and T. Yamashita Regulation of Axonal Elongation and Pathfinding from the Entorhinal Cortex to the Dentate Gyrus in the Hippocampus by the Chemokine Stromal Cell-Derived Factor 1{alpha} J. Neurosci., August 13, 2008; 28(33): 8344 - 8353. [Abstract] [Full Text] [PDF]

				S. Conrad, H. Genth, F. Hofmann, I. Just, and T. Skutella Neogenin-RGMa Signaling at the Growth Cone Is Bone Morphogenetic Protein-independent and Involves RhoA, ROCK, and PKC J. Biol. Chem., June 1, 2007; 282(22): 16423 - 16433. [Abstract] [Full Text] [PDF]

				A.-S. Zhang, S. A. Anderson, K. R. Meyers, C. Hernandez, R. S. Eisenstein, and C. A. Enns Evidence That Inhibition of Hemojuvelin Shedding in Response to Iron Is Mediated through Neogenin J. Biol. Chem., April 27, 2007; 282(17): 12547 - 12556. [Abstract] [Full Text] [PDF]

				D. Kuninger, R. Kuns-Hashimoto, R. Kuzmickas, and P. Rotwein Complex biosynthesis of the muscle-enriched iron regulator RGMc J. Cell Sci., August 15, 2006; 119(16): 3273 - 3283. [Abstract] [Full Text] [PDF]

				L.-R. You, N. Takamoto, C.-T. Yu, T. Tanaka, T. Kodama, F. J. DeMayo, S. Y. Tsai, and M.-J. Tsai Mouse lacking COUP-TFII as an animal model of Bochdalek-type congenital diaphragmatic hernia PNAS, November 8, 2005; 102(45): 16351 - 16356. [Abstract] [Full Text] [PDF]

				A.-S. Zhang, A. P. West Jr., A. E. Wyman, P. J. Bjorkman, and C. A. Enns Interaction of Hemojuvelin with Neogenin Results in Iron Accumulation in Human Embryonic Kidney 293 Cells J. Biol. Chem., October 7, 2005; 280(40): 33885 - 33894. [Abstract] [Full Text] [PDF]

				J. L. Babitt, Y. Zhang, T. A. Samad, Y. Xia, J. Tang, J. A. Campagna, A. L. Schneyer, C. J. Woolf, and H. Y. Lin Repulsive Guidance Molecule (RGMa), a DRAGON Homologue, Is a Bone Morphogenetic Protein Co-receptor J. Biol. Chem., August 19, 2005; 280(33): 29820 - 29827. [Abstract] [Full Text] [PDF]

				T. A. Samad, A. Rebbapragada, E. Bell, Y. Zhang, Y. Sidis, S.-J. Jeong, J. A. Campagna, S. Perusini, D. A. Fabrizio, A. L. Schneyer, et al. DRAGON, a Bone Morphogenetic Protein Co-receptor J. Biol. Chem., April 8, 2005; 280(14): 14122 - 14129. [Abstract] [Full Text] [PDF]

Home  |   Search  |   Archive  |   Subscribe  |   Contact  |   Help