Cellular and molecular neuroembryology
During development of the nervous system, specific connections are formed between different regions of the brain. The retinotectal projection is a model system well suited for studying the problems of axon guidance and target recognition. This projection is established by the growth of retinal axons to the optic tectum, their primary target, where they then form a topographic map. As axons from different regions of the retina must connect to specific regions in the tectum, multiple guidance factors and cell recognition molecules are postulated to be involved in this process.
In vitro studies have shown that axons from the temporal retina are specifically guided by factors present in the posterior half of the tectum. Attempts to identify these factors have led to the identification of two molecules, one of which has been recently cloned (Ephrin-A5, formerly RAGS for repulsive axon guidance signal). Ephrin-A5, a GPI-anchored protein with an apparent molecular weight of 25 kDa, is a member of the family of ligands for Eph-receptor-tyrosine kinases. The second molecule, RGM (for repulsive guidance molecule), is also GPI-linked but has a slightly higher molecular weight of 33-35 kDa .
Present work concentrates 1.) on the functional characterization of Ephrin-A5, its receptors and related molecules in vitro. 2.) on the development of a new technique to produce artificial concentration gradients of purified proteins.
Prof. Dr. Friedrich Bonhoeffer
(Dr. Jürgen Löschinger)
Weinl, C., Drescher, U., Lang, S., Bonhoeffer, F., and Loeschinger, J. On the turning of Xenopus retinal axons induced by ephrin-A5. Development 130 in press.
Loeschinger, J., Weth, F., Bonhoeffer, F. Reading of concentration gradients by axonal growth cones.The Royal Society, Proceedings: Biological Sciences, in press
Monnier, P., Sierra, A., Macchi, P:, Deitinghoff, A., Andersen, J.S., Mann, M., Flad, M., Hornberger, M., Stahl, B., Bonhoeffer, F., and Mueller, B.K. (2002) RGM is a repulsive guidance molecule for retinal axons. Nature, 419, 392-395
Fricke, C., Lee, J.S., Bonhoeffer, F., Geiger-Rudolph, S., and Chien, C.-B. (2001) astray, a zebrafish Roundabout required for retnal axon pathfinding. Science 292, 507-510.
Rosentreter, S.M. Davenport, R.W. Loschinger, J. Huf, J. Jung, J. Bonhoeffer, F. 1998. Response of retinal ganglion cell axons to striped linear gradients of repellent guidance molecules. Journal of Neurobiology 37(4), 541-62.