Axonal growth and guidance defects in Frizzled3 knock-out mice

A comparison of diffusion tensor magnetic resonance imaging, neurofilament staining, and genetically directed cell labeling

Yanshu Wang, Jiangyang Zhang, Susumu Mori, Jeremy Nathans

Research output: Contribution to journalArticle

Abstract

Previous work has identified axonal outgrowth and/or guidance defects in the brain and spinal cord of prenatal Frizzled3 (Fz3)-/- mice. To systematically explore the axonal defects in Fz3-/- mice and to compare techniques for the global assessment of axon tracts in the developing mouse, we have analyzed wild-type and Fz3-/- brains using (1) diffusion tensor magnetic resonance imaging (μDTI), (2) neurofilament staining, and (3) two genetically directed neuronal labeling methods. Confirming and extending the previous work of Wanget al. (2002), we find that the following structures/tracts are absent or greatly reduced in the Fz3 -/- brain: the anterior commissure, cerebral peduncle (corticospinal tract), corpus callosum, fornix, internal capsule (thalamocortical and corticothalamic tracts), stria medullaris, stria terminalis, and hippocampal commissure. An aberrant U-shaped fiber bundle immediately caudal to the optic tract connects the left and right sides of the Fz3-/- thalamus and likely represents a default pathway for thalamic axons that failed to enter the internal capsule. At embryonic day 18, labeling of cortical pyramidal cells with a yellow fluorescent protein reporter reveals widespread fragmentation of axons with no apparent loss of pyramidal cell bodies. Fragmentation likely represents one stage in the process that normally eliminates stalled or mistargeted axons. This work demonstrates the usefulness of μDTI and genetically directed neuronal labeling for the analysis of nervous system defects in the mouse.

Original languageEnglish (US)
Pages (from-to)355-364
Number of pages10
JournalJournal of Neuroscience
Volume26
Issue number2
DOIs
StatePublished - Jan 11 2006

Fingerprint

Diffusion Magnetic Resonance Imaging
Intermediate Filaments
Knockout Mice
Axons
Staining and Labeling
Internal Capsule
Pyramidal Cells
Growth
Brain Fornix
Pyramidal Tracts
Corpus Callosum
Brain
Systems Analysis
Thalamus
Nervous System
Spinal Cord
Proteins

Keywords

  • Axon guidance
  • Axonal fragmentation
  • Brain development
  • Cre recombinase
  • Diffusion tensor
  • Fiber tracts
  • Frizzled3
  • Knock-out mice
  • Magnetic resonance imaging
  • YFP

ASJC Scopus subject areas

  • Neuroscience(all)

Cite this

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title = "Axonal growth and guidance defects in Frizzled3 knock-out mice: A comparison of diffusion tensor magnetic resonance imaging, neurofilament staining, and genetically directed cell labeling",
abstract = "Previous work has identified axonal outgrowth and/or guidance defects in the brain and spinal cord of prenatal Frizzled3 (Fz3)-/- mice. To systematically explore the axonal defects in Fz3-/- mice and to compare techniques for the global assessment of axon tracts in the developing mouse, we have analyzed wild-type and Fz3-/- brains using (1) diffusion tensor magnetic resonance imaging (μDTI), (2) neurofilament staining, and (3) two genetically directed neuronal labeling methods. Confirming and extending the previous work of Wanget al. (2002), we find that the following structures/tracts are absent or greatly reduced in the Fz3 -/- brain: the anterior commissure, cerebral peduncle (corticospinal tract), corpus callosum, fornix, internal capsule (thalamocortical and corticothalamic tracts), stria medullaris, stria terminalis, and hippocampal commissure. An aberrant U-shaped fiber bundle immediately caudal to the optic tract connects the left and right sides of the Fz3-/- thalamus and likely represents a default pathway for thalamic axons that failed to enter the internal capsule. At embryonic day 18, labeling of cortical pyramidal cells with a yellow fluorescent protein reporter reveals widespread fragmentation of axons with no apparent loss of pyramidal cell bodies. Fragmentation likely represents one stage in the process that normally eliminates stalled or mistargeted axons. This work demonstrates the usefulness of μDTI and genetically directed neuronal labeling for the analysis of nervous system defects in the mouse.",
keywords = "Axon guidance, Axonal fragmentation, Brain development, Cre recombinase, Diffusion tensor, Fiber tracts, Frizzled3, Knock-out mice, Magnetic resonance imaging, YFP",
author = "Yanshu Wang and Jiangyang Zhang and Susumu Mori and Jeremy Nathans",
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AU - Zhang, Jiangyang

AU - Mori, Susumu

AU - Nathans, Jeremy

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KW - YFP

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