Semaphorins III and IV repel hippocampal axons via two distinct receptors

TLDR

Semaphorins are a large family of repulsive axon guidance molecules that bind neuropilin receptors to repel sensory, sympathetic, and motor axons. During development, Sema III, Sema IV, and their receptors Neuropilin‑1 and Neuropilin‑2 are expressed in the hippocampal formation. CA1, CA3, and dentate gyrus axons are repelled by entorhinal and neocortical tissues, with Sema III and Sema IV each strongly repelling these axons; entorhinal axons respond only to Sema III, and blocking Neuropilin‑1 abolishes Sema III but not Sema IV repulsion, demonstrating that these axons are guided by two distinct semaphorins through separate receptors.

Abstract

ABSTRACT The semaphorins are the largest family of repulsive axon guidance molecules. Secreted semaphorins bind neuropilin receptors and repel sensory, sympathetic and motor axons. Here we show that CA1, CA3 and dentate gyrus axons from E15-E17 mouse embryo explants are selectively repelled by entorhinal cortex and neocortex. The secreted semaphorins Sema III and Sema IV and their receptors Neuropilin-1 and -2 are expressed in the hippocampal formation during appropriate stages. Sema III and Sema IV strongly repel CA1, CA3 and dentate gyrus axons; entorhinal axons are only repelled by Sema III. An antibody against Neuropilin-1 blocks the repulsive action of Sema III and the entorhinal cortex, but has no effect on Sema IV-induced repulsion. Thus, chemorepulsion plays a role in axon guidance in the hippocampus, secreted semaphorins are likely to be responsible for this action, and the same axons can be repelled by two distinct semaphorins via two different receptors.