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 responses in vitro. To understand the role of Sema3F in the establishment of neural circuitry in vivo, we have generated sema3F null and sema3F conditional mutant mice. Inspection of the peripheral nervous system in sema3F null mice reveals that Sema3F is essential for the proper organization of specific cranial nerve projections. Analysis of the CNS in sema3F null mice reveals a crucial role for Sema3F in the rostral forebrain, midbrain, and hippocampus in establishing specific Npn-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 events in vivo and is a critical determinant of limbic and peripheral nervous system circuitry.
Sahay
Amar
A
Department of Neuroscience, Howard Hughes Medical Institute, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205, USA.
Molliver
Mark E
ME
Ginty
David D
DD
Kolodkin
Alex L
AL
D000679:Amygdala / Q000378:metabolism; D000818:Animals; D001369:Axons / Q000502:physiology; D015815:Cell Adhesion Molecules / Q000378:metabolism; D002490:Central Nervous System / Q000196:embryology / Q000378:metabolism*; D003391:Cranial Nerves / Q000196:embryology / Q000378:metabolism; D018390:Gene Targeting; D006624:Hippocampus / Q000196:embryology / Q000378:metabolism; D008024:Ligands; D008032:Limbic System / Q000196:embryology / Q000378:metabolism*; D008565:Membrane Proteins / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D008636:Mesencephalon / Q000196:embryology / Q000378:metabolism; D051379:Mice; D018345:Mice, Knockout; D008817:Mice, Mutant Strains; D009415:Nerve Net / Q000196:embryology / Q000378:metabolism*; D009419:Nerve Tissue Proteins / Q000172:deficiency / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D009474:Neurons / Q000378:metabolism*; D039943:Neuropilin-2 / Q000172:deficiency / Q000235:genetics / Q000378:metabolism; D016548:Prosencephalon / Q000196:embryology / Q000378:metabolism; D016704:Synapsins / Q000378:metabolism
D015815:Cell Adhesion Molecules; D008024:Ligands; D008565:Membrane Proteins; D009419:Nerve Tissue Proteins; D039943:Neuropilin-2; C491229:Sema3f protein, mouse; D016704:Synapsins; C091529:plexin