Progression from Mitotic Catastrophe to Germ Cell Death in Caenorhabditis Elegans Lis-1 Mutants Requires the Spindle Checkpoint

Overview

Journal Dev Biol

Publisher Elsevier

Specialties Biology
Reproductive Medicine

Date 2007 Mar 23

PMID 17376425

Citations 5

Authors

Edgar A Buttner

Aleksandra J Gil-Krzewska

Anandita K Rajpurohit

Craig P Hunter

Affiliations

Soon will be listed here.

Abstract

Deletion of the lissencephaly disease gene LIS-1 in humans causes an extreme disorganization of the brain associated with significant reduction in cortical neurons. Here we show that deletion or RNA interference (RNAi) of Caenorhabditis elegans lis-1 results in a reduction in germline nuclei and causes a variety of cellular, developmental, and neurological defects throughout development. Our analysis of the germline defects suggests that the reduction in nuclei number stems from dysfunctional mitotic spindles resulting in cell cycle arrest and eventually programmed cell death (apoptosis). Deletion of the spindle checkpoint gene mdf-1 blocks lis-1(lf)-induced cell cycle arrest and germline apoptosis, placing the spindle checkpoint pathway upstream of the programmed cell death pathway. These results suggest that apoptosis may contribute to the cell-sparse pathology of lissencephaly.

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References

Kitagawa R, Rose A . Components of the spindle-assembly checkpoint are essential in Caenorhabditis elegans. Nat Cell Biol. 1999; 1(8):514-21. DOI: 10.1038/70309. View

Siller K, Serr M, Steward R, Hays T, Doe C . Live imaging of Drosophila brain neuroblasts reveals a role for Lis1/dynactin in spindle assembly and mitotic checkpoint control. Mol Biol Cell. 2005; 16(11):5127-40. PMC: 1266413. DOI: 10.1091/mbc.e05-04-0338. View

Hsu J, Sun Z, Li X, Reuben M, Tatchell K, Bishop D . Mitotic phosphorylation of histone H3 is governed by Ipl1/aurora kinase and Glc7/PP1 phosphatase in budding yeast and nematodes. Cell. 2000; 102(3):279-91. DOI: 10.1016/s0092-8674(00)00034-9. View

Smith D, Niethammer M, Ayala R, Zhou Y, Gambello M, Wynshaw-Boris A . Regulation of cytoplasmic dynein behaviour and microtubule organization by mammalian Lis1. Nat Cell Biol. 2000; 2(11):767-75. DOI: 10.1038/35041000. View

Liu Z, Steward R, Luo L . Drosophila Lis1 is required for neuroblast proliferation, dendritic elaboration and axonal transport. Nat Cell Biol. 2000; 2(11):776-83. DOI: 10.1038/35041011. View

Faulkner N, Dujardin D, Tai C, Vaughan K, OConnell C, Wang Y . A role for the lissencephaly gene LIS1 in mitosis and cytoplasmic dynein function. Nat Cell Biol. 2000; 2(11):784-91. DOI: 10.1038/35041020. View

Swan A, Nguyen T, Suter B . Drosophila Lissencephaly-1 functions with Bic-D and dynein in oocyte determination and nuclear positioning. Nat Cell Biol. 1999; 1(7):444-9. DOI: 10.1038/15680. View

Michel L, Liberal V, Chatterjee A, Kirchwegger R, Pasche B, Gerald W . MAD2 haplo-insufficiency causes premature anaphase and chromosome instability in mammalian cells. Nature. 2001; 409(6818):355-9. DOI: 10.1038/35053094. View

Sasaki S, Shionoya A, Ishida M, Gambello M, Yingling J, Wynshaw-Boris A . A LIS1/NUDEL/cytoplasmic dynein heavy chain complex in the developing and adult nervous system. Neuron. 2001; 28(3):681-96. DOI: 10.1016/s0896-6273(00)00146-x. View

10.

Zhou Z, Hartwieg E, Horvitz H . CED-1 is a transmembrane receptor that mediates cell corpse engulfment in C. elegans. Cell. 2001; 104(1):43-56. DOI: 10.1016/s0092-8674(01)00190-8. View

11.

Maeda I, Kohara Y, Yamamoto M, Sugimoto A . Large-scale analysis of gene function in Caenorhabditis elegans by high-throughput RNAi. Curr Biol. 2001; 11(3):171-6. DOI: 10.1016/s0960-9822(01)00052-5. View

12.

Reddien P, Cameron S, Horvitz H . Phagocytosis promotes programmed cell death in C. elegans. Nature. 2001; 412(6843):198-202. DOI: 10.1038/35084096. View

13.

STERN B, Murray A . Lack of tension at kinetochores activates the spindle checkpoint in budding yeast. Curr Biol. 2001; 11(18):1462-7. DOI: 10.1016/s0960-9822(01)00451-1. View

14.

Wojcik E, Basto R, Serr M, Scaerou F, Karess R, HAYS T . Kinetochore dynein: its dynamics and role in the transport of the Rough deal checkpoint protein. Nat Cell Biol. 2001; 3(11):1001-7. DOI: 10.1038/ncb1101-1001. View

15.

Howell B, McEwen B, Canman J, Hoffman D, Farrar E, Rieder C . Cytoplasmic dynein/dynactin drives kinetochore protein transport to the spindle poles and has a role in mitotic spindle checkpoint inactivation. J Cell Biol. 2002; 155(7):1159-72. PMC: 2199338. DOI: 10.1083/jcb.200105093. View

16.

Li D, Roberts R . WD-repeat proteins: structure characteristics, biological function, and their involvement in human diseases. Cell Mol Life Sci. 2002; 58(14):2085-97. PMC: 11337334. DOI: 10.1007/pl00000838. View

17.

Huang N, Mootz D, Walhout A, Vidal M, Hunter C . MEX-3 interacting proteins link cell polarity to asymmetric gene expression in Caenorhabditis elegans. Development. 2002; 129(3):747-59. DOI: 10.1242/dev.129.3.747. View

18.

Garigan D, Hsu A, Fraser A, Kamath R, Ahringer J, Kenyon C . Genetic analysis of tissue aging in Caenorhabditis elegans: a role for heat-shock factor and bacterial proliferation. Genetics. 2002; 161(3):1101-12. PMC: 1462187. DOI: 10.1093/genetics/161.3.1101. View

19.

Hofmann E, Milstein S, Boulton S, Ye M, Hofmann J, Stergiou L . Caenorhabditis elegans HUS-1 is a DNA damage checkpoint protein required for genome stability and EGL-1-mediated apoptosis. Curr Biol. 2002; 12(22):1908-18. DOI: 10.1016/s0960-9822(02)01262-9. View

20.

Yan X, Li F, Liang Y, Shen Y, Zhao X, Huang Q . Human Nudel and NudE as regulators of cytoplasmic dynein in poleward protein transport along the mitotic spindle. Mol Cell Biol. 2003; 23(4):1239-50. PMC: 141156. DOI: 10.1128/MCB.23.4.1239-1250.2003. View