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The Journal of Neuroscience, January 28, 2004, 24(4):808-818; doi:10.1523/JNEUROSCI.4610-03.2004
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Development/Plasticity/Repair
Repulsive Guidance Molecule (RGM) Gene Function Is Required for Neural Tube Closure But Not Retinal Topography in the Mouse Visual System
Vera Niederkofler,1 * Rishard Salie,1 * Markus Sigrist,1 andSilvia Arber1,2 1Biozentrum, Department of Cell Biology, University of Basel, 4056 Basel, Switzerland, and 2Friedrich Miescher Institute, 4058 Basel, Switzerland
The establishment of topographic projections in the developing visual system depends on the spatially and temporally controlled expression of axon guidance molecules. In the developing chick tectum, the graded expression of the repulsive guidance molecule (RGM) has been proposed to be involved in controlling the topography of the retinal ganglion cell (RGC) axon termination zones along the anteroposterior axis of the tectum. We now show that there are three mouse proteins homologous to chick RGM displaying similar proteolytic processing but exhibiting differential cell-surface targeting by glycosyl phosphatidylinositol anchor addition. Two members of this gene family (mRGMa and mRGMb) are expressed in complementary patterns in the nervous system, and mRGMa is expressed prominently in the superior colliculus at the time of anteroposterior targeting of RGC axons. The third member of the family (mRGMc) is expressed almost exclusively in skeletal muscles. Functional studies in the mouse reveal a role for mRGMa in controlling cephalic neural tube closure, thus defining an unexpected role for mRGMa in early embryonic development. In contrast, mRGMa mutant mice did not exhibit defects in anteroposterior targeting of RGC axons to their stereotypic termination zones in the superior colliculus.
Key words: RGM; retinal topography; exencephaly; neural tube closure; GPI; axon guidance
Received Oct 15, 2003; revised November 19, 2003; accepted November 21, 2003.
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