title: Dorsal turning of motor corticospinal axons at the pyramidal decussation requires plexin signaling.
abstract: BACKGROUND
  The development of the corticospinal tract (CST) in higher vertebrates relies on a series of axon guidance decisions along its long projection pathway. Several guidance molecules are known to be involved at various decision points to regulate the projection of CST axons. However, previous analyses of the CST guidance defects in mutant mice lacking these molecules have suggested that there are other molecules involved in CST axon guidance that are yet to be identified. In this study, we investigate the role of plexin signaling in the guidance of motor CST axons in vivo.
  
  
  RESULTS
  Expression pattern studies show that plexin-A3, plexin-A4, and neuropilin-1 are expressed in the developing cerebral cortex when the motor CST axons originating from layer V cortical neurons are guided down to the spinal cord. By analyzing mutant mice, we show that motor CST axons that turn dorsally to cross the midline at the pyramidal decussation require plexin-A3 and plexin-A4 signaling. Although other CST guidance defects are found in neuropilin-1 mutants, this dorsal turning defect is not observed in either neuropilin-1 or neuropilin-2 mutants, suggesting that the local cues that activate plexin signaling at the dorsal turning point are membrane-bound semaphorins. Further expression pattern study and mutant analysis indicate that Sema6A is one of the local cues for motor CST axon turning at the pyramidal decussation.
  
  
  CONCLUSIONS
  Dorsal turning and midline crossing at the pyramidal decussation is a crucial step to properly direct CST axons into the dorsal spinal cord. We show that the signaling of plexin-A3, plexin-A4, and Sema6A is at least partially required for dorsal turning of the CST axons, while neuropilin-1 is required for proper fasciculation of the tract at midline crossing. Together with previous reports, these results demonstrate that several guidance cues are specifically utilized to regulate the dorsal turning and midline crossing of developing CST axons.
authors: Center for Neuroscience, University of California, Davis, California, 95618, USA. rlfaulkner@ucdavis.edu
authors: Regina L
authors: RL
authors: Faulkner
authors: Lawrence K
authors: LK
authors: Low
authors: Xiao-Bo
authors: XB
authors: Liu
authors: Jeffrey
authors: J
authors: Coble
authors: Edward G
authors: EG
authors: Jones
authors: Hwai-Jong
authors: HJ
authors: Cheng
mesh_terms: D000367:Age Factors; D000818:Animals; D001369:Axons / Q000378:metabolism*; D003598:Cytoskeletal Proteins; D018507:Gene Expression Regulation, Developmental; D006023:Glycoproteins / Q000235:genetics / Q000378:metabolism; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism; D051379:Mice; D018345:Mice, Knockout; D009046:Motor Neurons / Q000378:metabolism* / Q000648:ultrastructure; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism*; D039942:Neuropilin-1 / Q000235:genetics / Q000378:metabolism; D039943:Neuropilin-2 / Q000235:genetics / Q000378:metabolism; D017966:Pyramidal Cells / Q000378:metabolism / Q000648:ultrastructure; D011712:Pyramidal Tracts / Q000166:cytology / Q000254:growth & development / Q000378:metabolism; D011956:Receptors, Cell Surface / Q000235:genetics / Q000378:metabolism*; D040121:Semaphorin-3A / Q000235:genetics / Q000378:metabolism; D039961:Semaphorins / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction / Q000502:physiology
chemical_list: D003598:Cytoskeletal Proteins; D006023:Glycoproteins; D008565:Membrane Proteins; D009419:Nerve Tissue Proteins; D039943:Neuropilin-2; C492112:Plxna3 protein, mouse; C492110:Plxna4 protein, mouse; D011956:Receptors, Cell Surface; C488217:Sema3a protein, mouse; C111150:Sema3e protein, mouse; C504203:Sema6a protein, mouse; D040121:Semaphorin-3A; D039961:Semaphorins; D039942:Neuropilin-1