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Hum Mol Genet. 2012 Apr 15;21(8):1681-92. doi: 10.1093/hmg/ddr603. Epub 2011 Dec 21.

Tau's role in the developing brain: implications for intellectual disability.

Author information

1
Department of Molecular Genetics, Weizmann Institute of Science, 76100 Rehovot, Israel.

Abstract

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.

PMID:
22194194
DOI:
10.1093/hmg/ddr603
[Indexed for MEDLINE]

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