IN-VITRO GUIDANCE OF RETINAL GANGLION-CELL AXONS BY RAGS, A 25 KDA TECTAL PROTEIN RELATED TO LIGANDS FOR EPH RECEPTOR TYROSINE KINASES

The results of previous in vitro experiments indicate that a glycosylp hosphatidylinositol (GPl)-anchored protein may play an important role in the guidance of temporal retinal axons during the formation of the topographically ordered retinotectal projection. We have purified and cloned a GPl-anchored, 25 kDa glycoprotein that is a good candidate fo r a molecule involved in this process. During the time of innervation by retinal ganglion cells, this protein is gradedly expressed in the p osterior part of the developing tectum, In two different in vitro assa y systems, the recombinant protein induces growth cone collapse and re pulsion of retinal ganglion cell axons. These phenomena are observed f or axons of temporal as well as nasal origin, indicating that an addit ional activity may be necessary to confer the nasotemporal specificity observed in previous assays, We named the protein RAGS (for repulsive axon guidance signal), The sequence of RAGS shows significant homolog y to recently identified ligands for receptor tyrosine kinases of the Eph subfamily.