| Doublecortin-like kinase controls neurogenesis by regulating mitotic spindles and M phase progression. | |
MedLine Citation:
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PMID: 16387637 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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The mechanisms controlling neurogenesis during brain development remain relatively unknown. Through a differential protein screen with developmental versus mature neural tissues, we identified a group of developmentally enriched microtubule-associated proteins (MAPs) including doublecortin-like kinase (DCLK), a protein that shares high homology with doublecortin (DCX). DCLK, but not DCX, is highly expressed in regions of active neurogenesis in the neocortex and cerebellum. Through a dynein-dependent mechanism, DCLK regulates the formation of bipolar mitotic spindles and the proper transition from prometaphase to metaphase during mitosis. In cultured cortical neural progenitors, DCLK RNAi Lentivirus disrupts the structure of mitotic spindles and the progression of M phase, causing an increase of cell-cycle exit index and an ectopic commitment to a neuronal fate. Furthermore, both DCLK gain and loss of function in vivo specifically promote a neuronal identity in neural progenitors. These data provide evidence that DCLK controls mitotic division by regulating spindle formation and also determines the fate of neural progenitors during cortical neurogenesis. |
Authors:
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Tianzhi Shu; Huang-Chun Tseng; Tamar Sapir; Patrick Stern; Ying Zhou; Kamon Sanada; Andre Fischer; Frédéric M Coquelle; Orly Reiner; Li-Huei Tsai |
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Publication Detail:
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Type: Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't |
Journal Detail:
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Title: Neuron Volume: 49 ISSN: 0896-6273 ISO Abbreviation: Neuron Publication Date: 2006 Jan |
Date Detail:
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Created Date: 2006-01-02 Completed Date: 2006-02-14 Revised Date: 2009-11-19 |
Medline Journal Info:
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Nlm Unique ID: 8809320 Medline TA: Neuron Country: United States |
Other Details:
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Languages: eng Pagination: 25-39 Citation Subset: IM |
Affiliation:
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Department of Pathology, Harvard Medical School, Boston, Massachusetts 02115, USA. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Animals Cell Differentiation / physiology Cell Division / physiology* Cells, Cultured Cerebral Cortex / embryology Dyneins / physiology Embryonic Development / physiology Humans Mice Microtubule-Associated Proteins / metabolism Microtubules / physiology Mitosis / physiology Mitotic Spindle Apparatus / physiology* Nervous System / embryology* Neurons / cytology*, physiology* Prometaphase / physiology Protein-Serine-Threonine Kinases / metabolism, physiology* Stem Cells / metabolism |
| Grant Support | |
ID/Acronym/Agency:
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NS37007/NS/NINDS NIH HHS; R03TW007048/TW/FIC NIH HHS |
| Chemical | |
Reg. No./Substance:
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0/Microtubule-Associated Proteins; EC 2.7.1.-/Dcamkl1 protein, mouse; EC 2.7.11.1/Protein-Serine-Threonine Kinases; EC 3.6.4.2/Dyneins |
| Comments/Corrections | |
Comment In:
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Neuron. 2006 Jan 5;49(1):3-4
[PMID:
16387632
]
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From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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