The extracellular matrix in selective decussation of retinal ganglion cell axons: β2 laminins regulate the ipsilateral projection

AbstractIn binocular animals, retinal ganglion cell (RGC) axons selectively decussate at the optic chiasm. Selective decussation is directed by radial glia and midline neurons in the optic chiasm. Radial glia attach to the underlying pial basement membrane (PBM) that is rich in {beta}2 laminins. Here, we asked whether {beta}2 laminins in the PBM control the selective decussation of RGC axons. Genetic deletion of the {beta}2 subunit increased the proportion of non-decussating RGC axons in the ipsilateral tract. {beta}2 laminins are expressed in the PBM during the peak and late phases of RGC axon growth, and their deletion results in fragmentation of the PBM and dysmorphic radial glia. Consistent with the increase in the proportion of ipsilateral axons, we found persistent expression of the ipsilateral guidance cue EphrinB2 in radial glia during the late phase of axonal decussation, thus extending the developmental window for the development of the ipsilateral projection. Surprisingly, this increase in EphrinB2 was accompanied by an increase in the number of ipsilateral RGCs in the ventrotemporal retina. These results suggest that {beta}2 laminins regulate the size of the ipsilateral projection by providing cues that control the generation of ipsilateral RGCs and the expression of the ipsilateral cue EphrinB2 in the optic chiasm. Together, these findings position {beta}2 laminins as a novel regulator of the ipsilateral projection.