| 603 |
A
Role for Nr-CAM in the Patterning of Binocular Visual Pathways |
Scott
E. Williams, Martin Grumet, David R. Colman, Mark Henkemeyer,
Carol A. Mason, and Takeshi Sakurai |
Retinal
ganglion cell (RGC), optic chiasm, cell adhesion, binocular visual pathways |
For retina-chiasm cocultures,
retinal explants were plated onto 12 mm glass coverslip-bottom dishes (MatTek) coated sequentially
with 0.01% polyornithine (Sigma) and 10 mg/ml (E14.5) or 20 mg/ml
(E17.5) mouse laminin (Invitrogen) for 2 hr each at 37șC.
|
dissecting
microscope |
mouse |
|
ipsilateral
retina |
| |
Retinal ganglion cell (RGC) axons diverge within the
optic chiasm to project to opposite sides of the brain. In mouse, contralateral RGCs are distributed
throughout the retina, whereas ipsilateral RGCs are restricted to the ventrotemporal crescent
(VTC). While repulsive guidance mechanisms play a major role in the formation of the ipsilateral
projection, little is known about the contribution of growth-promoting interactions to the formation
of binocular visual projections. Here, we show that the cell adhesion molecule Nr-CAM is expressed
by RGCs that project contralaterally and is critical for the guidance of late-born RGCs within
the VTC. Blocking Nr-CAM function causes an increase in the size of the ipsilateral projection
and reduces neurite outgrowth on chiasm cells in an age- and region-specific manner. Finally,
we demonstrate that EphB1/ephrin-B2-mediated repulsion and Nr-CAMmediated attraction comprise
distinct molecular programs that each contributes to the proper formation of binocular visual
pathways. |
|