Neuroepithelial stem cell proliferation requires LIS1 for precise spindle orientation and symmetric division.
Mitotic spindle orientation and plane of cleavage in mammals is a determinant of whether division yields progenitor expansion and/or birth of new neurons during radial glial progenitor cell (RGPC) neurogenesis, but its role earlier in neuroepithelial stem cells is poorly understood. Here we report that Lis1 is essential for precise control of mitotic spindle orientation in both neuroepithelial stem cells and radial glial progenitor cells. Controlled gene deletion of Lis1 in vivo in neuroepithelial stem cells, where cleavage is uniformly vertical and symmetrical, provokes rapid apoptosis of those cells, while radial glial progenitors are less affected. Impaired cortical microtubule capture via loss of cortical dynein causes astral and cortical microtubules to be greatly reduced in Lis1-deficient cells. Increased expression of the LIS/dynein binding partner NDEL1 restores cortical microtubule and dynein localization in Lis1-deficient cells. Thus, control of symmetric division, essential for neuroepithelial stem cell proliferation, is mediated through spindle orientation determined via LIS1/NDEL1/dynein-mediated cortical microtubule capture.
Yingling
Jessica
J
Departments of Pediatrics and Medicine, Center for Human Genetics and Genomics, UCSD School of Medicine, 9500 Gilman Drive, La Jolla, CA 92098-0627, USA.
Youn
Yong Ha
YH
Darling
Dawn
D
Toyo-Oka
Kazuhito
K
Pramparo
Tiziano
T
Hirotsune
Shinji
S
Wynshaw-Boris
Anthony
A
D043203:1-Alkyl-2-acetylglycerophosphocholine Esterase / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D001921:Brain / Q000166:cytology / Q000196:embryology; D002453:Cell Cycle; D002465:Cell Movement; D049109:Cell Proliferation; D004398:Dyneins / Q000378:metabolism; D004622:Embryo, Mammalian / Q000166:cytology* / Q000378:metabolism; D005347:Fibroblasts / Q000166:cytology; D051379:Mice; D018345:Mice, Knockout; D008869:Microtubule-Associated Proteins / Q000235:genetics / Q000378:metabolism*; D008870:Microtubules / Q000378:metabolism; D008954:Models, Biological; D046569:Neuroepithelial Cells / Q000166:cytology*; D009474:Neurons / Q000166:cytology; D008941:Spindle Apparatus / Q000378:metabolism*; D013234:Stem Cells / Q000166:cytology*
D008869:Microtubule-Associated Proteins; D043203:1-Alkyl-2-acetylglycerophosphocholine Esterase; C513190:Pafah1b1 protein, mouse; D004398:Dyneins