TY - JOUR
T1 - Axonal growth and guidance defects in Frizzled3 knock-out mice
T2 - A comparison of diffusion tensor magnetic resonance imaging, neurofilament staining, and genetically directed cell labeling
AU - Wang, Yanshu
AU - Zhang, Jiangyang
AU - Mori, Susumu
AU - Nathans, Jeremy
PY - 2006/1/11
Y1 - 2006/1/11
N2 - 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.
AB - 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.
KW - Axon guidance
KW - Axonal fragmentation
KW - Brain development
KW - Cre recombinase
KW - Diffusion tensor
KW - Fiber tracts
KW - Frizzled3
KW - Knock-out mice
KW - Magnetic resonance imaging
KW - YFP
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UR - http://www.scopus.com/inward/citedby.url?scp=32544453658&partnerID=8YFLogxK
U2 - 10.1523/JNEUROSCI.3221-05.2006
DO - 10.1523/JNEUROSCI.3221-05.2006
M3 - Article
C2 - 16407530
AN - SCOPUS:32544453658
SN - 0270-6474
VL - 26
SP - 355
EP - 364
JO - Journal of Neuroscience
JF - Journal of Neuroscience
IS - 2
ER -