title: Variable laterality of corticospinal tract axons that regenerate after spinal cord injury as a result of PTEN deletion or knock-down.
abstract: Corticospinal tract (CST) axons from one hemisphere normally extend and terminate predominantly in the contralateral spinal cord. We previously showed that deleting the gene phosphatase and tensin homolog (PTEN) in the sensorimotor cortex enables CST axons to regenerate after spinal cord injury and that some regenerating axons extend along the "wrong" side. Here, we characterize the degree of specificity of regrowth in terms of laterality. PTEN was selectively deleted via cortical adeno-associated virus (AAV)-Cre injections in neonatal PTEN-floxed mice. As adults, mice received dorsal hemisection injuries at T12 or complete crush injuries at T9. CST axons from one hemisphere were traced by unilateral biotinylated dextran amine (BDA) injections in PTEN-deleted mice with spinal cord injury and in noninjured PTEN-floxed mice that had not received AAV-Cre. In noninjured mice, 97.9 ± 0.7% of BDA-labeled axons in white matter and 88.5 ± 1.0% of BDA-labeled axons in gray matter were contralateral to the cortex of origin. In contrast, laterality of CST axons that extended past a lesion due to PTEN deletion varied across animals. In some cases, regenerated axons extended predominantly on the ipsilateral side; in other cases, axons extended predominantly contralaterally, and in others, axons were similar in numbers on both sides. Similar results were seen in analyses of cases from previous studies using short hairpin (sh)RNA-mediated PTEN knock-down. These results indicate that CST axons that extend past a lesion due to PTEN deletion or knock-down do not maintain the contralateral rule of the noninjured CST, highlighting one aspect of how the resultant circuitry from regenerating axons may differ from that of the uninjured CST. J. Comp. Neurol. 524:2654-2676, 2016. © 2016 Wiley Periodicals, Inc.
authors.affiliation: Reeve-Irvine Research Center, University of California Irvine, Irvine, California, 92697.|Department of Anatomy & Neurobiology, University of California Irvine, Irvine, California, 92697.|School of Medicine, University of California San Diego, La Jolla, California, 92093.
authors.forename: Rafer
authors.initials: R
authors.lastname: Willenberg
authors.affiliation: F.M. Kirby Neurobiology Center, Children's Hospital, and Department of Neurology, Harvard Medical School, Boston, Massachusetts, 02115.|Institute for Antiviral Research, Department of Animal, Dairy, and Veterinary Sciences, Utah State University, Logan, Utah, 84322.
authors.forename: Katherine
authors.initials: K
authors.lastname: Zukor
authors.affiliation: F.M. Kirby Neurobiology Center, Children's Hospital, and Department of Neurology, Harvard Medical School, Boston, Massachusetts, 02115.|Division of Life Science, State Key Laboratory of Molecular Neuroscience, The Hong Kong University of Science and Technology, Clear Water Bay, Kowloon, Hong Kong, China, 999077.
authors.forename: Kai
authors.initials: K
authors.lastname: Liu
authors.affiliation: F.M. Kirby Neurobiology Center, Children's Hospital, and Department of Neurology, Harvard Medical School, Boston, Massachusetts, 02115.
authors.forename: Zhigang
authors.initials: Z
authors.lastname: He
authors.affiliation: Reeve-Irvine Research Center, University of California Irvine, Irvine, California, 92697.|Department of Anatomy & Neurobiology, University of California Irvine, Irvine, California, 92697.|Department of Neurobiology & Behavior, University of California Irvine, Irvine, California, 92697.|Department of Neurosurgery, University of California Irvine, Irvine, California, 92697.
authors.forename: Oswald
authors.initials: O
authors.lastname: Steward
mesh_terms: D000818:Animals; D001369:Axons / Q000737:chemistry / Q000502:physiology*; D005260:Female; D007839:Functional Laterality / Q000502:physiology*; D055785:Gene Knockdown Techniques / Q000379:methods; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D009416:Nerve Regeneration / Q000502:physiology*; D051059:PTEN Phosphohydrolase / Q000172:deficiency* / Q000235:genetics; D011712:Pyramidal Tracts / Q000737:chemistry / Q000502:physiology*; D013119:Spinal Cord Injuries / Q000235:genetics / Q000378:metabolism*
chemical_list: D051059:PTEN Phosphohydrolase; C487757:Pten protein, mouse
keywords: CST; RRID: AB_10013382; RRID: AB_2174349; SCI; axon regeneration