Agenesis of the corpus callosum in Nogo receptor deficient mice

Research output: Contribution to journalArticle

Abstract

The corpus callosum (CC) is the largest fiber tract in the mammalian brain, linking the bilateral cerebral hemispheres. CC development depends on the proper balance of axon growth cone attractive and repellent cues leading axons to the midline and then directing them to the contralateral hemisphere. Imbalance of these cues results in CC agenesis or dysgenesis. Nogo receptors (NgR1, NgR2, and NgR3) are growth cone directive molecules known for inhibiting axon regeneration after injury. We report that mice lacking Nogo receptors (NgR123-null mice) display complete CC agenesis due to axon misdirection evidenced by ectopic axons including cortical Probst bundles. Because glia and glial-derived growth cone repellent factors (especially the diffusible factor Slit2) are required for CC development, their distribution was studied. Compared with wild-type mice, NgR123-null mice had a sharp increase in the glial marker glial fibrillary acidic protein (GFAP) and in Slit2 at the glial wedge and indusium griseum, midline structures required for CC formation. NgR123-null mice displayed reduced motor coordination and hyperactivity. These data are consistent with the hypotheses that Nogo receptors are membrane-bound growth cone repellent factors required for migration of axons across the midline at the CC, and that their absence results directly or indirectly in midline gliosis, increased Slit2, and complete CC agenesis. J. Comp. Neurol., 2016.

Original languageEnglish (US)
JournalJournal of Comparative Neurology
DOIs
StateAccepted/In press - 2016

Fingerprint

Agenesis of Corpus Callosum
Axons
Growth Cones
Corpus Callosum
Neuroglia
Cues
Hyperkinesis
Gliosis
Glial Fibrillary Acidic Protein
Cerebrum
Nogo Receptors
Regeneration
Membranes
Wounds and Injuries
Brain

Keywords

  • Axon
  • Corpus callosum
  • Glia
  • NgR
  • Probst bundle
  • Slit2

ASJC Scopus subject areas

  • Neuroscience(all)

Cite this

@article{0e06ac10f6bd49e29302c5df94646764,
title = "Agenesis of the corpus callosum in Nogo receptor deficient mice",
abstract = "The corpus callosum (CC) is the largest fiber tract in the mammalian brain, linking the bilateral cerebral hemispheres. CC development depends on the proper balance of axon growth cone attractive and repellent cues leading axons to the midline and then directing them to the contralateral hemisphere. Imbalance of these cues results in CC agenesis or dysgenesis. Nogo receptors (NgR1, NgR2, and NgR3) are growth cone directive molecules known for inhibiting axon regeneration after injury. We report that mice lacking Nogo receptors (NgR123-null mice) display complete CC agenesis due to axon misdirection evidenced by ectopic axons including cortical Probst bundles. Because glia and glial-derived growth cone repellent factors (especially the diffusible factor Slit2) are required for CC development, their distribution was studied. Compared with wild-type mice, NgR123-null mice had a sharp increase in the glial marker glial fibrillary acidic protein (GFAP) and in Slit2 at the glial wedge and indusium griseum, midline structures required for CC formation. NgR123-null mice displayed reduced motor coordination and hyperactivity. These data are consistent with the hypotheses that Nogo receptors are membrane-bound growth cone repellent factors required for migration of axons across the midline at the CC, and that their absence results directly or indirectly in midline gliosis, increased Slit2, and complete CC agenesis. J. Comp. Neurol., 2016.",
keywords = "Axon, Corpus callosum, Glia, NgR, Probst bundle, Slit2",
author = "Yoo, {Seung Wan} and Motari, {Mary G.} and Schnaar, {Ronald Lee}",
year = "2016",
doi = "10.1002/cne.24064",
language = "English (US)",
journal = "Journal of Comparative Neurology",
issn = "0021-9967",
publisher = "Wiley-Liss Inc.",

}

TY - JOUR

T1 - Agenesis of the corpus callosum in Nogo receptor deficient mice

AU - Yoo, Seung Wan

AU - Motari, Mary G.

AU - Schnaar, Ronald Lee

PY - 2016

Y1 - 2016

N2 - The corpus callosum (CC) is the largest fiber tract in the mammalian brain, linking the bilateral cerebral hemispheres. CC development depends on the proper balance of axon growth cone attractive and repellent cues leading axons to the midline and then directing them to the contralateral hemisphere. Imbalance of these cues results in CC agenesis or dysgenesis. Nogo receptors (NgR1, NgR2, and NgR3) are growth cone directive molecules known for inhibiting axon regeneration after injury. We report that mice lacking Nogo receptors (NgR123-null mice) display complete CC agenesis due to axon misdirection evidenced by ectopic axons including cortical Probst bundles. Because glia and glial-derived growth cone repellent factors (especially the diffusible factor Slit2) are required for CC development, their distribution was studied. Compared with wild-type mice, NgR123-null mice had a sharp increase in the glial marker glial fibrillary acidic protein (GFAP) and in Slit2 at the glial wedge and indusium griseum, midline structures required for CC formation. NgR123-null mice displayed reduced motor coordination and hyperactivity. These data are consistent with the hypotheses that Nogo receptors are membrane-bound growth cone repellent factors required for migration of axons across the midline at the CC, and that their absence results directly or indirectly in midline gliosis, increased Slit2, and complete CC agenesis. J. Comp. Neurol., 2016.

AB - The corpus callosum (CC) is the largest fiber tract in the mammalian brain, linking the bilateral cerebral hemispheres. CC development depends on the proper balance of axon growth cone attractive and repellent cues leading axons to the midline and then directing them to the contralateral hemisphere. Imbalance of these cues results in CC agenesis or dysgenesis. Nogo receptors (NgR1, NgR2, and NgR3) are growth cone directive molecules known for inhibiting axon regeneration after injury. We report that mice lacking Nogo receptors (NgR123-null mice) display complete CC agenesis due to axon misdirection evidenced by ectopic axons including cortical Probst bundles. Because glia and glial-derived growth cone repellent factors (especially the diffusible factor Slit2) are required for CC development, their distribution was studied. Compared with wild-type mice, NgR123-null mice had a sharp increase in the glial marker glial fibrillary acidic protein (GFAP) and in Slit2 at the glial wedge and indusium griseum, midline structures required for CC formation. NgR123-null mice displayed reduced motor coordination and hyperactivity. These data are consistent with the hypotheses that Nogo receptors are membrane-bound growth cone repellent factors required for migration of axons across the midline at the CC, and that their absence results directly or indirectly in midline gliosis, increased Slit2, and complete CC agenesis. J. Comp. Neurol., 2016.

KW - Axon

KW - Corpus callosum

KW - Glia

KW - NgR

KW - Probst bundle

KW - Slit2

UR - http://www.scopus.com/inward/record.url?scp=84978219610&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84978219610&partnerID=8YFLogxK

U2 - 10.1002/cne.24064

DO - 10.1002/cne.24064

M3 - Article

C2 - 27339102

AN - SCOPUS:84978219610

JO - Journal of Comparative Neurology

JF - Journal of Comparative Neurology

SN - 0021-9967

ER -