Document Type
Article
Subject Area(s)
Biology
Abstract
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 dyneindependent 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.
Digital Object Identifier (DOI)
https://doi.org/10.1083/jcb.200803071
Publication Info
The Journal of Cell Biology, Volume 182, Issue 6, 2008, pages 1063-1071.
Rights
© 2008, the authors.
Originally published in the Journal of Cell Biology by the Rockefeller University Press.
APA Citation
Hebbar, S., Mesngon, M., Guillote, A., Desai, B., Ayala, R., & Smith, D. (2008). Lis1 and Ndel1 Influence the Timing of Nuclear Envelope Breakdown in Neural Stem Cells. The Journal of Cell Biology, 182(6), 1063–1071. https://doi.org/10.1083/jcb.200803071