Semaphorins III and IV repel hippocampal axons via two distinct receptors

The semaphorins are the largest family of repulsive axon guidance molecules , Secreted semaphorins bind neuropilin receptors and repel sensory, sympath etic and motor axons. Here we show that CA1, CA3 and dentate gyrus axons fr om E15-E17 mouse embryo explants are selectively repelled by entorhinal cor tex and neocortex, The secreted semaphorins Sema III and Sema IV and their receptors Neuropilin-1 and -2 are expressed in the hippocampal formation du ring appropriate stages. Sema III and Sema IV strongly repel CA1, CA3 and d entate gyrus axons; entorhinal axons are only repelled by Sema III. An anti body against Neuropilin-1 blocks the repulsive action of Sema III and the e ntorhinal cortex, but has no effect on Sema IV-induced repulsion. Thus, che morepulsion plays a role in axon guidance in the hippocampus, secreted sema phorins are likely to be responsible for this action, and the same axons ca n be repelled by two distinct semaphorins via two different receptors.