Tau's role in the developing brain: implications for intellectual disability.
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Tau's role in the developing brain: implications for intellectual disability. / Sapir, Tamar; Frotscher, Michael; Levy, Talia; Mandelkow, Eva-Maria; Reiner, Orly.
In: HUM MOL GENET, Vol. 21, No. 8, 8, 2012, p. 1681-1692.Research output: SCORING: Contribution to journal › SCORING: Journal article › Research › peer-review
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TY - JOUR
T1 - Tau's role in the developing brain: implications for intellectual disability.
AU - Sapir, Tamar
AU - Frotscher, Michael
AU - Levy, Talia
AU - Mandelkow, Eva-Maria
AU - Reiner, Orly
PY - 2012
Y1 - 2012
N2 - 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.
AB - 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.
M3 - SCORING: Journal article
VL - 21
SP - 1681
EP - 1692
JO - HUM MOL GENET
JF - HUM MOL GENET
SN - 0964-6906
IS - 8
M1 - 8
ER -