Our efforts to uncover mechanisms that drive synaptic targeting focus on the developing visual system. Specifically, we are interested in how synapses are formed between retinal ganglion cells (RGCs), the output neurons of the retina, and target neurons within the brain. Spurred on by Roger Sperry’s postulation of the chemoaffinity hypothesis (which postulated that regionalized chemical cues direct topographic mapping of RGC axons within the brain), many groups have searched for and identified chemical/molecular cues necessary for the correct exiting of retinal ganglion cell axons from the retina, the correct crossing of RGC axons at the optic chiasm, the repulsion of RGC axons from non-retinal targets, and the topographic mapping of RGC axons within the lateral geniculate nucleus (LGN) and superior colliculus (SC). Despite these monumental advances, it still remains unclear how different classes of retinal ganglion cells (RGCs)– of which there are more than 30 – target functionally distinct nuclei within the brain. One brain region where class-specific targeting of RGC axons is most evident is the LGN – a thalamic relay nucleus that contains three structurally and functionally distinct subnuclei: the ventral and dorsal LGN (vLGN and dLGN, respectively) and the intergeniculate leaflet that separates them. Since different classes of RGCs target either vLGN and IGL or dLGN, we hypothesized that regionalized guidance cues must exist in the LGN to direct axonal targeting. We have identified many candidate molecules that may act as class-specific targeting cues for retinogeniculate targeting and are now testing their necessity and sufficiency in retinogeniculate circuit formation.
Retinal projections to the mouse LGN labeled by cholera toxin B. Axons from the ipsilateral eye are shown in green and those from the contralateral eye are shown in red. Note the mistargeted retinal axons (arrowheads) in reeler mutants (reln rl/rl), which lack functional reelin protein. (Images adapted from Su et al. 2013; see also Su et al. 2011, Fox and Guido 2011)