Lis1 and Ndel1 influence the timing of nuclear envelope breakdown in neural stem cells

Lis1 and Ndel1 are essential for animal development. They interact directly with one another and with cytoplasmic dynein. The developing brain is especially sensitive to reduced Lis1 or Ndel1 levels, as both proteins influence spindle orientation, neural cell fate decisions, and neuronal migration....

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Bibliographic Details
Published in:The Journal of cell biology 2008-09, Vol.182 (6), p.1063-1071
Main Authors: Hebbar, Sachin, Mesngon, Mariano T, Guillotte, Aimee M, Desai, Bhavim, Ayala, Ramses, Smith, Deanna S
Format: Article
Language:English
Subjects:
1-Alkyl-2-acetylglycerophosphocholine Esterase - genetics
1-Alkyl-2-acetylglycerophosphocholine Esterase - metabolism
Animals
Antibodies
Biochemistry
Brain
Carrier Proteins - genetics
Carrier Proteins - metabolism
Cell Cycle - physiology
Cell Line
Cell lines
Cercopithecus aethiops
COS Cells
Dynactin Complex
Dyneins - metabolism
Embryonic stem cells
Female
Humans
Kidney cells
Male
Mice
Microtubule-Associated Proteins - genetics
Microtubule-Associated Proteins - metabolism
Microtubules - metabolism
Neural stem cells
Neurons
Neurons - cytology
Neurons - physiology
Nocodazole - metabolism
Nuclear Envelope - metabolism
Phosphorylation
Prophase
Protein Binding
Proteins
Rats
Rodents
Stem cells
Stem Cells - cytology
Stem Cells - metabolism
Tubulin Modulators - metabolism
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Summary:Lis1 and Ndel1 are essential for animal development. They interact directly with one another and with cytoplasmic dynein. The developing brain is especially sensitive to reduced Lis1 or Ndel1 levels, as both proteins influence spindle orientation, neural cell fate decisions, and neuronal migration. We report here that Lis1 and Ndel1 reduction in a mitotic cell line impairs prophase nuclear envelope (NE) invagination (PNEI). This dynein-dependent process facilitates NE breakdown (NEBD) and occurs before the establishment of the bipolar spindle. Ndel1 phosphorylation is important for this function, regulating binding to both Lis1 and dynein. Prophase cells in the ventricular zone (VZ) of embryonic day 13.5 Lis1⁺/⁻ mouse brains show reduced PNEI, and the ratio of prophase to prometaphase cells is increased, suggesting an NEBD delay. Moreover, prophase cells in the VZ contain elevated levels of Ndel1 phosphorylated at a key cdk5 site. Our data suggest that a delay in NEBD in the VZ could contribute to developmental defects associated with Lis1-Ndel1 disruption.
ISSN:0021-9525
1540-8140
DOI:10.1083/jcb.200803071