Abstract
The potential role of doublecortin (Dcx), encoding a microtubule-associated protein, in brain development has remained controversial. Humans with mutations show profound alterations in cortical lamination, whereas in mouse, RNAi-mediated knockdown but not germline knockout shows abnormal positioning of cortical neurons. Here, we report that the doublecortin-like kinase (Dclk) gene functions in a partially redundant pathway with Dcx in the formation of axonal projections across the midline and migration of cortical neurons. Dosage-dependent genetic effects were observed in both interhemispheric connectivity and migration of cortically and subcortically derived neurons. Surprisingly, RNAi-mediated knockdown of either gene results in similar migration defects. These results indicate the Dcx microtubule-associated protein family is required for proper neuronal migration and axonal wiring.
Publication types
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Research Support, N.I.H., Extramural
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Research Support, Non-U.S. Gov't
MeSH terms
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Agenesis of Corpus Callosum
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Aging / metabolism
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Aging / physiology
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Animals
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Animals, Newborn / growth & development
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Axons / metabolism
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Brain / abnormalities
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Brain / embryology*
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Brain / growth & development*
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Brain / metabolism
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Cell Movement / physiology*
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Cerebral Cortex / embryology
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Congenital Abnormalities / genetics
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Doublecortin Domain Proteins
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Doublecortin Protein
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Doublecortin-Like Kinases
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Embryo, Mammalian / pathology
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Embryonic Development
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Exons / physiology
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Gene Dosage
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Gene Targeting
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Mice
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Mice, Inbred Strains
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Mice, Knockout
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Microtubule-Associated Proteins / genetics
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Microtubule-Associated Proteins / physiology*
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Nerve Fibers / physiology*
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Neurons / metabolism
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Neurons / physiology*
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Neuropeptides / genetics
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Neuropeptides / physiology*
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Protein Serine-Threonine Kinases / deficiency
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Protein Serine-Threonine Kinases / genetics
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Protein Serine-Threonine Kinases / metabolism
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Protein Serine-Threonine Kinases / physiology*
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Protein Structure, Tertiary
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Synaptic Transmission / physiology
Substances
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DCX protein, human
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Dcx protein, mouse
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Doublecortin Domain Proteins
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Doublecortin Protein
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Microtubule-Associated Proteins
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Neuropeptides
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Doublecortin-Like Kinases
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Dclk1 protein, mouse
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Protein Serine-Threonine Kinases