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Experimental Genetics Group

Bolleke Abstract   Pijltje
Tau-4R suppresses proliferation and promotes neuronal differentiation in the hippocampus of tau knockin/knockout mice.

FASEB J. 2007 Jul;21(9):2149-61.

Sennvik K1*, Boekhoorn K2*, Lasrado R1*, Terwel D1, Verhaeghe S1, Korr H3, Schmitz C3, Tomiyama T4, Mori H4, Krugers H2, Joels M2, Ramakers GJ5, Lucassen PJ2, Van Leuven F1**.

1Experimental Genetics Group, Department Human Genetics, K.U.Leuven, Leuven, Belgium.
2Section Neurobiology, Swammerdam Institute of Life Sciences, Amsterdam, The Netherlands.
3Department of Anatomy and Cell Biology, Rheinland-Westfalen Technischen Hochschule University of Aachen, Aachen, Germany.
4Department of Neuroscience, Medical School, Osaka, Japan.
5Netherlands Institute for Brain Research, Amsterdam, The Netherlands.
*These authors contributed equally to this work.
**Corresponding author.

Differential isoform expression and phosphorylation of protein tau are believed to regulate the assembly and stabilization of microtubuli in fetal and adult neurons. To define the functions of tau in the developing and adult brain, we generated transgenic mice expressing the human tau-4R/2N (htau-4R) isoform on a murine tau null background, by a knockout/knockin approach (tau-KOKI). The main findings in these mice were the significant increases in hippocampal volume and neuronal number, which were sustained throughout adult life and paralleled by improved cognitive functioning. The increase in hippocampal size was found to be due to increased neurogenesis and neuronal survival. Proliferation and neuronal differentiation were further analyzed in primary hippocampal cultures from tau-KOKI mice, before and after htau-4R expression onset. In absence of tau, proliferation increased and both neurite and axonal outgrowth were reduced. Htau-4R expression suppressed proliferation, promoted neuronal differentiation, and restored neurite and axonal outgrowth. We suggest that the tau-4R isoform essentially contributes to hippocampal development by controlling proliferation and differentiation of neuronal precursors.

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