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The Journal of Neuroscience, September 26, 2007, 27(39):10345-10349; doi:10.1523/JNEUROSCI.2787-07.2007
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Brief Communications
Diffusion Tensor Magnetic Resonance Imaging and Tract-Tracing Analysis of Probst Bundle Structure in Netrin1- and DCC-Deficient Mice
Tianbo Ren,1 Jiangyang Zhang,2 Celine Plachez,1 Susumu Mori,2,3 andLinda J. Richards1,4 1Department of Anatomy and Neurobiology and The Program in Neuroscience, The University of Maryland School of Medicine, Baltimore, Maryland 21201, 2Department of Radiology, Division of NMR Research, and Department of Biomedical Engineering, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205, 3F. M. Kirby Research Center for Functional Brain Imaging, Kennedy Krieger Institute, Baltimore, Maryland 21205, and 4The School of Biomedical Sciences and The Queensland Brain Institute, The University of Queensland, Brisbane, Queensland 4072, Australia
Correspondence should be addressed to Dr. Linda J. Richards, The University of Queensland School of Biomedical Sciences and The Queensland Brain Institute, Otto Hirschfeld Building, Room 715, Brisbane, Queensland 4072, Australia. Email: richards{at}uq.edu.au
In many cases of callosal dysgenesis in both human patients and mouse models, misguided fibers from the cortex form abnormal bilateral, barrel-shaped structures known as Probst bundles. Because little is known about how axons are arranged within these anomalous fiber bundles, understanding this arrangement may provide structural and molecular insights into how axons behave when they are misguided in vivo. Previous studies described these bundles as longitudinal swirls of axons that fail to cross the midline (Ozaki et al., 1987). However, recent studies on human acallosal patients using diffusion tensor magnetic resonance imaging (DTMRI) technology suggest that axons project in an anteroposterior direction within the Probst bundle (Lee et al., 2004; Tovar-Moll et al., 2007). This led us to ask the question, is DTMRI an accurate method for analyzing axonal tracts in regions of high axon overlap and disorganization, or is our current perception of axon arrangement within these bundles inaccurate? Using DTMRI, immunohistochemistry, and carbocyanine dye tract-tracing studies, we analyzed the Probst bundles in both Netrin1 and deleted in colorectal cancer (DCC) mutant mice. Our findings indicate that DTMRI can accurately demonstrate fiber tract orientation and morphology where axons are in ordered arrays such as in the dorsal part of the bundle. In ventral areas, where the axons are disorganized, no coordinated diffusion is apparent via DTMRI. In these regions, a higher-resolution approach such as tract tracing is required. We conclude that in DCC and Netrin1 mutant mice, guidance mechanisms remain in the dorsal part of the tract but are lost ventrally.
Key words: corpus callosum; axon guidance; brain development; agenesis of the corpus callosum (ACC); cerebral cortex; magnetic resonance imaging
Received June 19, 2007; revised Aug. 4, 2007; accepted Aug. 7, 2007.
Correspondence should be addressed to Dr. Linda J. Richards, The University of Queensland School of Biomedical Sciences and The Queensland Brain Institute, Otto Hirschfeld Building, Room 715, Brisbane, Queensland 4072, Australia. Email: richards{at}uq.edu.au
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