Doublecortin-like Kinase Controls Neurogenesis by Regulating Mitotic Spindles and M Phase Progression.
From: Department of Pathology, Harvard Medical School, Boston, Massachusetts 02115, USA.
Neuron
- Publish Date: Jan 2006
- ISSN: 0896-6273
- Volume: 49
- Issue: 1
- Pages: 25-39
- Medium: Print
- Language: English
- Citation (JAMA): Shu Tianzhi, Tseng Huang-Chun, Sapir Tamar, et al. Doublecortin-like Kinase Controls Neurogenesis by Regulating Mitotic Spindles and M Phase Progression.. Neuron Jan 2006;49:25-39
Abstract
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.
Mesh Headings (Keywords): Animals, Cell Differentiation, Cell Division, Cells, Cultured, Cerebral Cortex, Dynein ATPase, Embryonic Development, Humans, Mice, Microtubule-Associated Proteins, Microtubules, Mitosis, Mitotic Spindle Apparatus, Nervous System, Neurons, Prometaphase, Protein-Serine-Threonine Kinases, Stem Cells
Check for Full Text / PubMed Unique Identifier (PMID): 16387637
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