Magnetic resonance diffusion tensor microimaging reveals a role for Bcl-x in brain development and homeostasis.
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.
Zhang
Jiangyang
J
Department of Radiology, Division of Nuclear Magnetic Resonance Research, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205, USA.
Chen
Ying-bei
YB
Hardwick
J Marie
JM
Miller
Michael I
MI
Plachez
Celine
C
Richards
Linda J
LJ
Yarowsky
Paul
P
van Zijl
Peter
P
Mori
Susumu
S
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
C494812:Bcl2l1 protein, mouse; D009419:Nerve Tissue Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; D051020:bcl-X Protein
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