The doublecortin and doublecortin-like kinase 1 genes cooperate in murine hippocampal development.
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.
Tanaka
Teruyuki
T
Neurogenetics Laboratory, Department of Neurosciences, University of California, San Diego, CA, USA.
Koizumi
Hiroyuki
H
Gleeson
Joseph G
JG
D000375:Aging / Q000473:pathology / Q000502:physiology*; D000818:Animals; D000831:Animals, Newborn; D019521:Body Patterning / Q000502:physiology; D002449:Cell Aggregation; D002454:Cell Differentiation; D002465:Cell Movement; D000089622:Doublecortin Domain Proteins; D000089662:Doublecortin Protein; D000089742:Doublecortin-Like Kinases; D006624:Hippocampus / Q000166:cytology* / Q000196:embryology* / Q000254:growth & development; D066298:In Vitro Techniques; D051379:Mice; D018345:Mice, Knockout; D008869:Microtubule-Associated Proteins / Q000378:metabolism*; D009415:Nerve Net / Q000166:cytology / Q000196:embryology / Q000254:growth & development; D009474:Neurons / Q000166:cytology* / Q000502:physiology; D009479:Neuropeptides / Q000378:metabolism*; D038081:Organogenesis / Q000502:physiology*; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism*
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