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Cerebral Cortex 2006 16(Supplement 1):i69-i73; doi:10.1093/cercor/bhk005
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Published by Oxford University Press 2006.

The Doublecortin and Doublecortin-Like Kinase 1 Genes Cooperate in Murine Hippocampal Development

Teruyuki Tanaka1, Hiroyuki Koizumi and Joseph G. Gleeson

Neurogenetics Laboratory, Department of Neurosciences, University of California, San Diego, CA, USA, 1 Current address: Department of Regenerative Biology and Medicine, National Research Institute for Child Health and Development, Setagaya-ku, Tokyo 157-8535, Japan

Address correspondence to Joseph G. Gleeson, LBR 3A16, 9500 Gilman Drive, La Jolla, CA 92093-0691, USA. Email: jogleeson{at}ucsd.edu.

The doublecortin (Dcx) and doublecortin-like kinase 1 (Dclk) genes are developmentally expressed neuronal microtubule-associated proteins. Humans with DCX mutations show a severe defect in hippocampal development, but targeted deletion in mouse shows only a defect in pyramidal neuron lamination. There is significant sequence overlap between Dcx and Dclk, suggesting functional redundancy. Here we show that the two genes display overlapping expression patterns in developing mouse hippocampus. Targeted deletion of Dclk shows no appreciable developmental defect in the hippocampus, but removal of both genes shows severe hippocampal lamination defects involving the entire cornu ammonis and dentate gyrus fields that mimic the human phenotype. These results suggest these genes are partially functionally redundant in the formation of the murine hippocampus.

Key Words: development • doublecortin • hippocampus • lissencephaly • subpial migratory stream


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