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.
Koizumi
Hiroyuki
H
Neurogenetics Laboratory, Department of Neurosciences, University of California, San Diego, La Jolla, California 93093, USA.
Tanaka
Teruyuki
T
Gleeson
Joseph G
JG
D061085:Agenesis of Corpus Callosum; D000375:Aging / Q000378:metabolism / Q000502:physiology; D000818:Animals; D000831:Animals, Newborn / Q000254:growth & development; D001369:Axons / Q000378:metabolism; D001921:Brain / Q000002:abnormalities / Q000196:embryology* / Q000254:growth & development* / Q000378:metabolism; D002465:Cell Movement / Q000502:physiology*; D002540:Cerebral Cortex / Q000196:embryology; D000013:Congenital Abnormalities / Q000235:genetics; D000089622:Doublecortin Domain Proteins; D000089662:Doublecortin Protein; D000089742:Doublecortin-Like Kinases; D004622:Embryo, Mammalian / Q000473:pathology; D047108:Embryonic Development; D005091:Exons / Q000502:physiology; D018628:Gene Dosage; D018390:Gene Targeting; D051379:Mice; D008815:Mice, Inbred Strains; D018345:Mice, Knockout; D008869:Microtubule-Associated Proteins / Q000235:genetics / Q000502:physiology*; D009412:Nerve Fibers / Q000502:physiology*; D009474:Neurons / Q000378:metabolism / Q000502:physiology*; D009479:Neuropeptides / Q000235:genetics / Q000502:physiology*; D017346:Protein Serine-Threonine Kinases / Q000172:deficiency / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D017434:Protein Structure, Tertiary; D009435:Synaptic Transmission / Q000502:physiology
C000714328:DCX protein, human; C000714847:Dcx protein, mouse; D000089622:Doublecortin Domain Proteins; D000089662:Doublecortin Protein; D008869:Microtubule-Associated Proteins; D009479:Neuropeptides; D000089742:Doublecortin-Like Kinases; C485525:Dclk1 protein, mouse; D017346:Protein Serine-Threonine Kinases