A contractile nuclear actin network drives chromosome congression in oocytes

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Chromosome capture by microtubules is widely accepted as the universal mechanism of spindle assembly in dividing cells. However, the observed length of spindle microtubules and computer simulations of spindle assembly predict that chromosome capture is efficient in small cells, but may fail in cells with large nuclear volumes such as animal oocytes. Here we investigate chromosome congression during the first meiotic division in starfish oocytes. We show that microtubules are not sufficient for capturing chromosomes. Instead, chromosome congression requires actin polymerization. After nuclear envelope breakdown, we observe the formation of a filamentous actin mesh in the nuclear region, and find that contraction of this network delivers chromosomes to the microtubule spindle. We show that this mechanism is essential for preventing chromosome loss and aneuploidy of the egg—a leading cause of pregnancy loss and birth defects in humans.

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Figure 1: Chromosomes congress without attachment to meiotic asters.
Figure 2: Chromosome congression is independent of microtubules but relies on actin polymerization.
Figure 3: Actin polymerization initiates at NEBD.
Figure 4: Actin polymerizes into a contractile network in the nuclear region that moves chromosomes to the animal pole.
Figure 5: F-actin-stabilizing drugs prevent chromosome movement and contraction of the actin network.


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Part of this work was performed at the Marine Biological Laboratory (MBL) in Woods Hole, supported by summer research fellowships from Nikon Inc. and the E. and M. Spiegel, F.B. and B.G. Bang, L.B. Lehmann, R.D. Allen and H.W. Rand foundations to J.E. Martin Hoppe and Leica Microsystems in Mannheim are gratefully acknowledged for providing equipment at the MBL. P.L. was supported by a predoctoral fellowship from the Louis-Jeantet Foundation. We would like to thank J. C. Bulinski for providing p3EGFP–EMTB, K. Weijer for EGFP–ABD and K. Ribbeck for fluorescently labelled Ran.

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Correspondence to Jan Ellenberg.

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Supplementary information

Suppplementary Figure and Video Legends

Text to accompany the below Supplementary Figures and Supplementary Videos. (DOC 27 kb)

Supplementary Figure S1

Effects of nocodazole and latrunculin B on the microtubule and actin cytoskeleton (PDF 685 kb)

Supplementary Figure S2

Low doses of LAB also strongly delay chromosome movement. (PDF 135 kb)

Supplementary Figure S3

DNA coated beads nucleate actin patches similar to chromosomes. (PDF 3558 kb)

Supplementary Video S1

Microtubules are too short to capture chromosomes in meiosis I of starfish oocytes. (MOV 3182 kb)

Supplementary Video S2

Chromosome congression in an untreated oocyte. (MOV 3124 kb)

Supplementary Video S3

Chromosome congression in an oocyte preincubated for 1h and matured in 3.3 µM nocodazole. (MOV 2188 kb)

Supplementary Video S4

Chromosome congression in an oocyte treated with 2 µM LAB 10 minutes before NEBD. (MOV 3573 kb)

Supplementary Video S5

Chromosome congression in an oocyte treated with 3.3 µM nocodazole and 250 nM LAB at the time of hormone addition. (MOV 4145 kb)

Supplementary Video S6

A contractile actin meshwork moves chromosomes to the animal pole in starfish oocytes. (MOV 5273 kb)

Supplementary Video S7

Details of the actin mesh. (MOV 2437 kb)

Supplementary Video S8

Phalloidin injection delays the collapse of the actin mesh. (MOV 1978 kb)

Supplementary Video S9

Chromosome congression in an oocyte treated with 120 nM LAB 10 minutes before NEBD. (MOV 1696 kb)

Supplementary Video S10

DNA coated beads nucleate actin patches similar to chromosomes. (MOV 1215 kb)

Supplementary Video S11

Uncoated beads do not nucleate actin. (MOV 2672 kb)

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Lénárt, P., Bacher, C., Daigle, N. et al. A contractile nuclear actin network drives chromosome congression in oocytes. Nature 436, 812–818 (2005) doi:10.1038/nature03810

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