New molecules for hippocampal development

Pathfinding by developing axons towards their proper targets is an essentia l step in establishing appropriate neuronal connections. Recent work involv ing cell culture assays and molecular biology strategies, including knockou t animals, strongly indicates that a complex network of guidance signals re gulates the formation of hippocampal connections during development. Outgro wing axons are routed towards the hippocampal formation by specific express ion of long-range cues, which include secreted class 3 semaphorins, netrin 1 and Slit proteins. Local membrane- or substrate-anchored molecules, such as ligands of the ephrin A subclass, provide layer-specific positional info rmation. Understanding the molecular mechanisms that underlie axonal guidan ce during hippocampal development might be of importance in making therapeu tic use of sprouting fibers, which are produced following the loss of affer ents in CNS lesion.