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The Journal of Neuroscience, October 18, 2006, 26(42):10868-10878; doi:10.1523/JNEUROSCI.3027-06.2006

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Development/Plasticity/Repair
Role of Bone Morphogenic Protein 2 in Retinal Patterning and Retinotectal Projection

Hiraki Sakuta, Hiroo Takahashi, Takafumi Shintani, Kazuma Etani, Akihiro Aoshima, and Masaharu Noda

Division of Molecular Neurobiology, National Institute for Basic Biology and School of Life Science, The Graduate University for Advanced Studies, Myodaiji-cho, Okazaki 444-8787, Japan

Correspondence should be addressed to Dr. Masaharu Noda, Division of Molecular Neurobiology, National Institute for Basic Biology, 5-1 Higashiyama, Myodaiji-cho, Okazaki 444-8787, Japan. Email: madon{at}nibb.ac.jp

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.

Key words: retina; retinotectal projection; BMP2; Ventroptin; ephrin-A2; chick

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Received March 16, 2006; revised Sept. 3, 2006; accepted Sept. 6, 2006.

Correspondence should be addressed to Dr. Masaharu Noda, Division of Molecular Neurobiology, National Institute for Basic Biology, 5-1 Higashiyama, Myodaiji-cho, Okazaki 444-8787, Japan. Email: madon{at}nibb.ac.jp

This article has been cited by other articles:

				D. T. Plas, O. S. Dhande, J. E. Lopez, D. Murali, C. Thaller, M. Henkemeyer, Y. Furuta, P. Overbeek, and M. C. Crair Bone Morphogenetic Proteins, Eye Patterning, and Retinocollicular Map Formation in the Mouse J. Neurosci., July 9, 2008; 28(28): 7057 - 7067. [Abstract] [Full Text] [PDF]

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