Doublecortin-like kinase functions with doublecortin to mediate fiber tract decussation and neuronal migration.
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.
Mesh Terms:
Aging, Animals, Animals, Newborn, Axons, Brain, Cell Movement, Cerebral Cortex, Congenital Abnormalities, Corpus Callosum, Embryo, Mammalian, Embryonic Development, Exons, Gene Dosage, Gene Targeting, Mice, Mice, Inbred Strains, Mice, Knockout, Microtubule-Associated Proteins, Nerve Fibers, Neurons, Neuropeptides, Protein Structure, Tertiary, Protein-Serine-Threonine Kinases, Synaptic Transmission
Aging, Animals, Animals, Newborn, Axons, Brain, Cell Movement, Cerebral Cortex, Congenital Abnormalities, Corpus Callosum, Embryo, Mammalian, Embryonic Development, Exons, Gene Dosage, Gene Targeting, Mice, Mice, Inbred Strains, Mice, Knockout, Microtubule-Associated Proteins, Nerve Fibers, Neurons, Neuropeptides, Protein Structure, Tertiary, Protein-Serine-Threonine Kinases, Synaptic Transmission
Neuron
Date: Jan. 05, 2006
PubMed ID: 16387639
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