A key role for GAP-43 in the retinotectal topographic organization

To have a proper spatial visual perception, vertebrate retinal ganglion cel ls connect 60 their brain targets in a highly ordered Fashion. The molecula r bases for such topographic retinotectal connection in mammals still remai n largely unknown. Using the gene knock-out approach in mice, we report her e a key role for the GAP-43 growth cone protein in the development of the v isual system. In mice bearing a targeted disruption of GAP-43 exon 1, a hig h proportion of retinal ganglion cell. (RGC) axons was found to grow abnorm ally into the ipsilateral optic tract and into the hypothalamus. After leav ing the optic chiasm during development, the GAP-iis-deficient RGC axons ge nerally follow the optic tracts but are unable to form proper terminal zone s in the lateral geniculate nucleus. Moreover, in the superior colliculus, RGC axons lacking GAP-43 are intermingled. These results suggest an essenti al role for GAP-43 in development of the topographic retinotectal connectio n. (C) 1999 Academic Press.