Semaphorin 3F Is Critical for Development of Limbic System Circuitry and Is Required in Neurons for Selective CNS Axon Guidance Events
Copyright policy )Semaphorin 3F Is Critical for Development of Limbic System Circuitry and Is Required in Neurons for Selective CNS Axon Guidance Events
Little is known about the role of class 3 semaphorins in the development of CNS circuitry. Several class 3 semaphorins, including semaphorin 3F (Sema3F) bind to the receptor neuropilin-2 to confer chemorepulsive responsesin vitro. To understand the role of Sema3F in the establishment of neural circuitryin vivo, we have generatedsema3Fnull andsema3Fconditional mutant mice. Inspection of the peripheral nervous system insema3Fnull mice reveals that Sema3F is essential for the proper organization of specific cranial nerve projections. Analysis of the CNS insema3Fnull mice reveals a crucial role for Sema3F in the rostral forebrain, midbrain, and hippocampus in establishing specificNpn-2(neuropilin-2)-expressing limbic tracts. Furthermore, we identify Sema3F and Npn-2 as the first guidance cue-receptor pair shown to be essential for controlling the development of amygdaloid circuitry. In addition, we provide genetic evidence in vertebrates for a neuronal requirement of a soluble axon guidance cue in CNS axon guidance. Our data reveal a requirement for neuronal Sema3F in the normal development of the anterior commissure in the ventral forebrain and infrapyramidal tract in the hippocampus. Thus, our results show that Sema3F is the principal ligand for Npn-2-mediated axon guidance eventsin vivoand is a critical determinant of limbic and peripheral nervous system circuitry.
- Howard Hughes Medical Institute United States
- Johns Hopkins Medicine United States
- Johns Hopkins University School of Medicine United States
Central Nervous System, Mice, Knockout, Neurons, Cranial Nerves, Membrane Proteins, Nerve Tissue Proteins, Amygdala, Ligands, Hippocampus, Axons, Mice, Mutant Strains, Neuropilin-2, Mice, Prosencephalon, Mesencephalon, Gene Targeting, Limbic System, Animals, Nerve Net, Cell Adhesion Molecules
Central Nervous System, Mice, Knockout, Neurons, Cranial Nerves, Membrane Proteins, Nerve Tissue Proteins, Amygdala, Ligands, Hippocampus, Axons, Mice, Mutant Strains, Neuropilin-2, Mice, Prosencephalon, Mesencephalon, Gene Targeting, Limbic System, Animals, Nerve Net, Cell Adhesion Molecules
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