title: Ectopic myelinating oligodendrocytes in the dorsal spinal cord as a consequence of altered semaphorin 6D signaling inhibit synapse formation.
abstract: Different types of sensory neurons in the dorsal root ganglia project axons to the spinal cord to convey peripheral information to the central nervous system. Whereas most proprioceptive axons enter the spinal cord medially, cutaneous axons typically do so laterally. Because heavily myelinated proprioceptive axons project to the ventral spinal cord, proprioceptive axons and their associated oligodendrocytes avoid the superficial dorsal horn. However, it remains unclear whether their exclusion from the superficial dorsal horn is an important aspect of neural circuitry. Here we show that a mouse null mutation of Sema6d results in ectopic placement of the shafts of proprioceptive axons and their associated oligodendrocytes in the superficial dorsal horn, disrupting its synaptic organization. Anatomical and electrophysiological analyses show that proper axon positioning does not seem to be required for sensory afferent connectivity with motor neurons. Furthermore, ablation of oligodendrocytes from Sema6d mutants reveals that ectopic oligodendrocytes, but not proprioceptive axons, inhibit synapse formation in Sema6d mutants. Our findings provide new insights into the relationship between oligodendrocytes and synapse formation in vivo, which might be an important element in controlling the development of neural wiring in the central nervous system.
authors.affiliation: Division of Developmental Biology, Cincinnati Children's Hospital Medical Center, Cincinnati, OH 45229, USA.
authors.forename: Jennifer R
authors.initials: JR
authors.lastname: Leslie
authors.forename: Fumiyasu
authors.initials: F
authors.lastname: Imai
authors.forename: Kaori
authors.initials: K
authors.lastname: Fukuhara
authors.forename: Noriko
authors.initials: N
authors.lastname: Takegahara
authors.forename: Tilat A
authors.initials: TA
authors.lastname: Rizvi
authors.forename: Roland H
authors.initials: RH
authors.lastname: Friedel
authors.forename: Fan
authors.initials: F
authors.lastname: Wang
authors.forename: Atsushi
authors.initials: A
authors.lastname: Kumanogoh
authors.forename: Yutaka
authors.initials: Y
authors.lastname: Yoshida
mesh_terms: D000818:Animals; D030801:Animals, Genetically Modified; D002828:Choristoma / Q000235:genetics*; D005727:Ganglia, Spinal / Q000378:metabolism / Q000473:pathology; D051379:Mice; D008954:Models, Biological; D009413:Nerve Fibers, Myelinated / Q000378:metabolism / Q000473:pathology; D055495:Neurogenesis / Q000235:genetics / Q000502:physiology; D009836:Oligodendroglia; D011434:Proprioception / Q000235:genetics; D039961:Semaphorins / Q000235:genetics* / Q000502:physiology; D011984:Sensory Receptor Cells / Q000378:metabolism / Q000473:pathology; D015398:Signal Transduction / Q000235:genetics / Q000502:physiology; D013116:Spinal Cord / Q000378:metabolism / Q000473:pathology; D013118:Spinal Cord Diseases / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D013569:Synapses / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D009435:Synaptic Transmission / Q000235:genetics / Q000502:physiology
chemical_list: C483479:Sema6d protein, mouse; D039961:Semaphorins