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. 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.
Hebbar
Sachin
S
Department of Biological Sciences, University of South Carolina, Columbia, SC 29208, USA.
Mesngon
Mariano T
MT
Guillotte
Aimee M
AM
Desai
Bhavim
B
Ayala
Ramses
R
Smith
Deanna S
DS
D043203:1-Alkyl-2-acetylglycerophosphocholine Esterase / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D019556:COS Cells; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism*; D002453:Cell Cycle / Q000502:physiology; D002460:Cell Line; D002522:Chlorocebus aethiops; D000072159:Dynactin Complex; D004398:Dyneins / Q000378:metabolism; D005260:Female; D006801:Humans; D008297:Male; D051379:Mice; D008869:Microtubule-Associated Proteins / Q000235:genetics / Q000378:metabolism*; D008870:Microtubules / Q000378:metabolism; D009474:Neurons / Q000166:cytology / Q000502:physiology; D015739:Nocodazole / Q000378:metabolism; D009685:Nuclear Envelope / Q000378:metabolism*; D010766:Phosphorylation; D011485:Protein Binding; D051381:Rats; D013234:Stem Cells / Q000166:cytology / Q000378:metabolism; D050257:Tubulin Modulators / Q000378:metabolism
D002352:Carrier Proteins; D000072159:Dynactin Complex; D008869:Microtubule-Associated Proteins; C486015:Ndel1 protein, mouse; D050257:Tubulin Modulators; D043203:1-Alkyl-2-acetylglycerophosphocholine Esterase; C513190:Pafah1b1 protein, mouse; D004398:Dyneins; D015739:Nocodazole