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The Journal of Neuroscience, February 23, 2005, 25(8):1881-1888; doi:10.1523/JNEUROSCI.4129-04.2005

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Cellular/Molecular
Magnetic Resonance Diffusion Tensor Microimaging Reveals a Role for Bcl-x in Brain Development and Homeostasis

Jiangyang Zhang,^1,3 Ying-bei Chen,² J. Marie Hardwick,^2,4 Michael I. Miller,^3,5 Celine Plachez,⁶ Linda J. Richards,⁶ Paul Yarowsky,⁷ Peter van Zijl,^1,8 and Susumu Mori^1,8

¹Department of Radiology, Division of Nuclear Magnetic Resonance Research and Departments of ²Pharmacology, ³Biomedical Engineering, and ⁴Molecular Microbiology and Immunology, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205, ⁵Center of Imaging Science, Johns Hopkins University, Baltimore, Maryland 21218, ⁶Department of Anatomy and Neurobiology and The Program in Neuroscience and ⁷Department of Pharmacology and Experimental Therapeutics, University of Maryland School of Medicine, Baltimore, Maryland 21201, and ⁸F. M. Kirby Research Center for Functional Brain Imaging, Kennedy Krieger Institute, Baltimore, Maryland 21205

A new technique based on diffusion tensor imaging and computational neuroanatomy was developed to efficiently and quantitatively characterize the three-dimensional morphology of the developing brains. The technique was used to analyze the phenotype of conditional Bcl-x knock-out mice, in which the bcl-x gene was deleted specifically in neurons of the cerebral cortex and hippocampus beginning at embryonic day 13.5 as cells became postmitotic. Affected brain regions and associated axonal tracts showed severe atrophy in adult Bcl-x-deficient mice. Longitudinal studies revealed that these phenotypes are established by regressive processes that occur primarily during the first postnatal week, whereas neurogenesis and migration showed no obvious abnormality during embryonic stages. Specific families of white matter tracts that once formed normally during the embryonic stages underwent dramatic degeneration postnatally. Thus, this technique serves as a powerful tool to efficiently localize temporal and spatial manifestation of morphological phenotype.

Key words: magnetic; resonance; diffusion; cortex; axon; development; phenotype

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Received Oct 5, 2004; revised December 18, 2004; accepted December 22, 2004.

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