title: Magnetic resonance diffusion tensor microimaging reveals a role for Bcl-x in brain development and homeostasis.
abstract: 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.
authors.affiliation: Department of Radiology, Division of Nuclear Magnetic Resonance Research, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205, USA.
authors.forename: Jiangyang
authors.initials: J
authors.lastname: Zhang
authors.forename: Ying-bei
authors.initials: YB
authors.lastname: Chen
authors.forename: J Marie
authors.initials: JM
authors.lastname: Hardwick
authors.forename: Michael I
authors.initials: MI
authors.lastname: Miller
authors.forename: Celine
authors.initials: C
authors.lastname: Plachez
authors.forename: Linda J
authors.initials: LJ
authors.lastname: Richards
authors.forename: Paul
authors.initials: P
authors.lastname: Yarowsky
authors.forename: Peter
authors.initials: P
authors.lastname: van Zijl
authors.forename: Susumu
authors.initials: S
authors.lastname: Mori
mesh_terms: D000818:Animals; D017209:Apoptosis; D001284:Atrophy; D002540:Cerebral Cortex / Q000002:abnormalities / Q000737:chemistry / Q000196:embryology / Q000254:growth & development* / Q000473:pathology; D003433:Crosses, Genetic; D038524:Diffusion Magnetic Resonance Imaging; D005804:Genes, Lethal; D005865:Gestational Age; D006624:Hippocampus / Q000002:abnormalities / Q000737:chemistry / Q000196:embryology / Q000254:growth & development* / Q000473:pathology; D006706:Homeostasis; D021621:Imaging, Three-Dimensional; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009186:Myelin Sheath / Q000473:pathology; D009410:Nerve Degeneration; D009419:Nerve Tissue Proteins / Q000032:analysis / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D010641:Phenotype; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000032:analysis / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D051020:bcl-X Protein
chemical_list: C494812:Bcl2l1 protein, mouse; D009419:Nerve Tissue Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; D051020:bcl-X Protein
references.citation: Annu Rev Biomed Eng. 2002;4:375-405
references.pmid: 12117763
references.citation: Comput Med Imaging Graph. 1999 Jan-Feb;23(1):15-24
references.pmid: 10091864
references.citation: J Magn Reson B. 1994 Mar;103(3):247-54
references.pmid: 8019776
references.citation: Magn Reson Med. 1994 Nov;32(5):592-601
references.pmid: 7808260
references.citation: Magn Reson Med. 1998 Oct;40(4):511-6
references.pmid: 9771567
references.citation: Ann Neurol. 1999 Feb;45(2):265-9
references.pmid: 9989633
references.citation: NMR Biomed. 2002 Nov-Dec;15(7-8):543-52
references.pmid: 12489100
references.citation: Neuroimage. 2003 Nov;20(3):1639-48
references.pmid: 14642474
references.citation: J Neurosci. 1998 Feb 15;18(4):1408-18
references.pmid: 9454850
references.citation: Magn Reson Imaging. 1997;15(4):433-40
references.pmid: 9223044
references.citation: Neuroimage. 2002 Apr;15(4):892-901
references.pmid: 11906229
references.citation: Radiology. 1990 Aug;176(2):439-45
references.pmid: 2367658
references.citation: J Magn Reson B. 1996 Jun;111(3):209-19
references.pmid: 8661285
references.citation: Science. 1995 Mar 10;267(5203):1506-10
references.pmid: 7878471
references.citation: Annu Rev Biomed Eng. 2003;5:119-45
references.pmid: 14527311
references.citation: Exp Neurol. 1991 Nov;114(2):145-83
references.pmid: 1748192
references.citation: Magn Reson Med. 1994 Nov;32(5):579-83
references.pmid: 7808259
references.citation: IEEE Trans Image Process. 2000;9(8):1357-70
references.pmid: 18262973
references.citation: Magn Reson Med. 2001 Jul;46(1):18-23
references.pmid: 11443706
references.citation: Mol Endocrinol. 2000 Jul;14(7):1038-52
references.pmid: 10894153
references.citation: Radiology. 1998 Oct;209(1):57-66
references.pmid: 9769812