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

To have a proper spatial visual perception, vertebrate retinal ganglion cells connect to their brain targets in a highly ordered fashion. The molecular bases for such topographic retinotectal connection in mammals still remain largely unknown. Using the gene knock-out approach in mice, we report here a key role for the GAP-43 growth cone protein in the development of the visual system. In mice bearing a targeted disruption of GAP-43 exon 1, a high proportion of retinal ganglion cell (RGC) axons was found to grow abnormally into the ipsilateral optic tract and into the hypothalamus. After leaving the optic chiasm during development, the GAP-43-deficient RGC axons generally follow the optic tracts but are unable to form proper terminal zones in the lateral geniculate nucleus. Moreover, in the superior colliculus, RGC axons lacking GAP-43 are intermingled. These results suggest an essential role for GAP-43 in development of the topographic retinotectal connection.