Taus role in the developing brain: implications for intellectual disability

Taus role in the developing brain: implications for intellectual disability
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DOI:
10.1093/hmg/ddr603
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发表时间:
2012-04-15
影响因子:
3.5
通讯作者:
Reiner, Orly
Reiner, Orly
中科院分区:
生物学2区
文献类型:
--
作者:
Sapir, Tamar;Frotscher, Michael;Reiner, Orly

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Microdeletions encompassing the MAPT (Tau) locus resulting in intellectual disability raised the hypothesis that Tau may regulate early functions in the developing brain. Our results indicate that neuronal migration was inhibited in mouse brains following Tau reduction. In addition, the leading edge of radially migrating neurons was aberrant in spite of normal morphology of radial glia. Furthermore, intracellular mitochondrial transport and morphology were affected. In early postnatal brains, a portion of Tau knocked down neurons reached the cortical plate. Nevertheless, they exhibited far less developed dendrites and a striking reduction in connectivity evident by the size of boutons. Our novel results strongly implicate MAPT as a dosage-sensitive gene in this locus involved in intellectual disability. Furthermore, our results are likely to impact our understanding of other diseases involving Tau.