Imaging, anatomical, and molecular analysis of callosal formation in the developing human fetal brain

Authors

  • Tianbo Ren,

    1. Department of Anatomy and Neurobiology and Program in Neuroscience, University of Maryland School of Medicine, Baltimore, Maryland
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  • Aurora Anderson,

    1. Department of Pediatrics, University of Maryland School of Medicine, Baltimore, Maryland
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  • Wei-Bin Shen,

    1. Department of Anatomy and Neurobiology and Program in Neuroscience, University of Maryland School of Medicine, Baltimore, Maryland
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  • Hao Huang,

    1. Department of Radiology, Division of NMR Research and Department of Biomedical Engineering, Johns Hopkins University School of Medicine, Baltimore, Maryland
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  • Celine Plachez,

    1. Department of Anatomy and Neurobiology and Program in Neuroscience, University of Maryland School of Medicine, Baltimore, Maryland
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  • Jiangyang Zhang,

    1. Department of Radiology, Division of NMR Research and Department of Biomedical Engineering, Johns Hopkins University School of Medicine, Baltimore, Maryland
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  • Susumu Mori,

    1. Department of Radiology, Division of NMR Research and Department of Biomedical Engineering, Johns Hopkins University School of Medicine, Baltimore, Maryland
    2. F.M. Kirby Research Center for Functional Brain Imaging, Kennedy Krieger Institute, Baltimore, Maryland
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  • Stephen L. Kinsman,

    1. Department of Pediatrics, University of Maryland School of Medicine, Baltimore, Maryland
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  • Linda J. Richards

    Corresponding author
    1. Department of Anatomy and Neurobiology and Program in Neuroscience, University of Maryland School of Medicine, Baltimore, Maryland
    2. University of Queensland School of Biomedical Sciences and Queensland Brain Institute, Brisbane, Queensland, Australia
    • University of Queensland School of Biomedical Sciences and Queensland Brain Institute, Otto Hirschfeld Building, Room 715, Brisbane, Queensland, 4072, Australia
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    • Fax: 61-7-3365-1299


Abstract

A complex set of axonal guidance mechanisms are utilized by axons to locate and innervate their targets. In the developing mouse forebrain, we previously described several midline glial populations as well as various guidance molecules that regulate the formation of the corpus callosum. Since agenesis of the corpus callosum is associated with over 50 different human congenital syndromes, we wanted to investigate whether these same mechanisms also operate during human callosal development. Here we analyze midline glial and commissural development in human fetal brains ranging from 13 to 20 weeks of gestation using both diffusion tensor magnetic resonance imaging and immunohistochemistry. Through our combined radiological and histological studies, we demonstrate the morphological development of multiple forebrain commissures/decussations, including the corpus callosum, anterior commissure, hippocampal commissure, and the optic chiasm. Histological analyses demonstrated that all the midline glial populations previously described in mouse, as well as structures analogous to the subcallosal sling and cingulate pioneering axons, that mediate callosal axon guidance in mouse, are also present during human brain development. Finally, by Northern blot analysis, we have identified that molecules involved in mouse callosal development, including Slit, Robo, Netrin1, DCC, Nfia, Emx1, and GAP-43, are all expressed in human fetal brain. These data suggest that similar mechanisms and molecules required for midline commissure formation operate during both mouse and human brain development. Thus, the mouse is an excellent model system for studying normal and pathological commissural formation in human brain development. © 2006 Wiley-Liss, Inc.

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