| The development of topographic maps in the nervous system has been intensely examined for decades. Topographic maps, in which one population of neurons connects to another such that neighbor relationships are maintained, are present throughout the brain and are a dominant organizational principle of the central nervous system. Nonetheless, the mechanisms and molecules controlling the development of a topographic map has not been elucidated to a significant extent. The projection from retinal ganglion cells to the optic tectum of chicks, frogs and fish, or the superior colliculus of rodents has served as the classic model system for experimentation. I use a variety of in vitro and in vivo techniques to identify molecular activities responsible, in part, for multiple aspects of retinotectal and retinocollicular mapping along both the anterior—posterior axis and the medial—lateral axis of the optic tectum and superior colliculus. I demonstrate that members of the EphA subgroup of receptor tyrosine kinases and their ligands, the ephrin-As, are expressed in patterns consistent with a role in retinotopic mapping. Furthermore, I show that EphA/ephrin-A interactions control aspects of topographic map formation along the anterior—posterior axis by preferentially inhibiting temporal retinal ganglion cell axon extension. In addition, ephrin-As inhibit interstitial branch formation along retinal ganglion cell axon shafts, a critical event in retinotopic mapping. I also provide evidence that members of the EphB subclass of Eph receptors and their ligand, ephrin-B1, are expressed in a pattern orthogonal to that observed for EphAs/ephrin-As, and are thus appropriately distributed to control, at least in part, retinotopic mapping along the medial—lateral axis. I demonstrate that EphBs are required to mediate interstitial axon branch extension medially, presumably via attractive interactions with ephrin-B1. In addition, I provide evidence for a second function of ephrin-B1 in repelling retinal ganglion cell interstitial branches when appropriate. I have, through a combination of in vitro and in vivo techniques involving the addition or subtraction of Eph/ephrin activity, determined the molecules and mechanisms responsible, in part, for multiple aspects of retinotectal map development in chick and retinocollicular map formation in mouse. |
