REGULATION OF TOPOGRAPHIC PROJECTION BY THE EPH FAMILY RECEPTOR BSK (EPHA5) AND ITS LIGANDS

Topographic projection is a general feature of brain architecture and is critical for appropriate information processing and coding. Neverth eless, little is known about the mechanisms that govern topographic or ganization. The Eph family receptor tyrosine kinases and ligands have recently been implicated in the specification of topographic maps. We have shown that Bsk, an Eph family receptor, and its ligands are expre ssed in a complementary fashion in neurons and targets, respectively, in several neural systems. For example, in the hippocampus, Bsk is exp ressed in an increasing lateral to medial gradient. In contrast, at le ast three different ligands, viz., Elf-1, LERK3/Ehk1-L, and AL-1/RAGS/ LERK7, are transcribed in complementary (opposing) gradients in the hi ppocampal subcortical target, the lateral septum. However, the spatial and temporal distribution of the ligands are different, such that com binatorially they specify the full target region during development. C onsistent with a key role in hippocamposeptal topographic projection, the ligands selectively inhibit the growth of the topographically inap propriate medial hippocampal neurites but sustain the growth of the ap propriate lateral neurites. Our studies indicate that the interaction of Bsk and its ligands restricts the receptor-positive medial neurons to the topographically appropriate, ligand-poor dorsal septal target. In addition to the hippocamposeptal system, Bsk and its ligands are al so expressed in afferents and targets of several other systems, includ ing the olfactory and the retinotectal systems. Consequently, Bsk and its ligands may play important roles in neuron-target interactions in multiple neural circuits.