title: DCC mediated axon guidance of spinal interneurons is essential for normal locomotor central pattern generator function.
abstract: Coordinated limb rhythmic movements take place through organized signaling in local spinal cord neuronal networks. The establishment of these circuitries during development is dependent on the correct guidance of axons to their targets. It has previously been shown that the well-known axon guidance molecule netrin-1 is required for configuring the circuitry that provides left-right alternating coordination in fictive locomotion. The attraction of commissural axons to the midline in response to netrin-1 has been shown to involve the netrin-1 receptor DCC (deleted in Colorectal Cancer). However, the role of DCC for the establishment of CPG coordination has not yet been resolved. We show that mice carrying a null mutation of DCC displayed an uncoordinated left-right activity during fictive locomotion accompanied by a loss of interneuronal subpopulations originating from commissural progenitors. Thus, DCC plays a crucial role in the formation of spinal neuronal circuitry coordinating left-right activities. Together with the previously published results from netrin-1 deficient mice, the data presented in this study suggest a role for the most ventral originating V3 interneurons in synchronous activities over the midline. Further, it provides evidence that axon crossing in the spinal cord is more intricately controlled than in previously suggested models of DCC-netrin-1 interaction.
authors.affiliation: Unit of Developmental Genetics, Department of Neuroscience, Uppsala University, Box 593, Husargatan 3, Uppsala 75124, Sweden.
authors.forename: Nadine
authors.initials: N
authors.lastname: Rabe Bernhardt
authors.forename: Fatima
authors.initials: F
authors.lastname: Memic
authors.forename: Henrik
authors.initials: H
authors.lastname: Gezelius
authors.forename: Anja-Lena
authors.initials: AL
authors.lastname: Thiebes
authors.forename: Anna
authors.initials: A
authors.lastname: Vallstedt
authors.forename: Klas
authors.initials: K
authors.lastname: Kullander
mesh_terms: D000818:Animals; D001369:Axons / Q000502:physiology* / Q000648:ultrastructure; D063226:Central Pattern Generators / Q000166:cytology / Q000502:physiology*; D007395:Interneurons / Q000502:physiology / Q000648:ultrastructure; D008124:Locomotion / Q000502:physiology; D051379:Mice; D000075386:Netrin Receptors; D011956:Receptors, Cell Surface / Q000502:physiology*; D015398:Signal Transduction; D013116:Spinal Cord / Q000196:embryology / Q000502:physiology*
chemical_list: D000075386:Netrin Receptors; D011956:Receptors, Cell Surface