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PMID: 10385520 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S.

Chromosomal influence on meiotic spindle assembly: abnormal meiosis I in female Mlh1 mutant mice.

The Journal of cell biology ·Vol. 145 ·No. 7 ·1999-06-28 ·Pages 1395-406

Woods LM, Hodges CA, Baart E, Baker SM, Liskay M, Hunt PA

Abstract

In mouse oocytes, the first meiotic spindle is formed through the action of multiple microtubule organizing centers rather than a pair of centrosomes. Although the chromosomes are thought to play a major role in organizing the meiotic spindle, it remains unclear how a stable bipolar spindle is established. We have studied the formation of the first meiotic spindle in murine oocytes from mice homozygous for a targeted disruption of the DNA mismatch repair gene, Mlh1. In the absence of the MLH1 protein meiotic recombination is dramatically reduced and, as a result, the vast majority of chromosomes are present as unpaired univalents at the first meiotic division. The orientation of these univalent chromosomes at prometaphase suggests that they are unable to establish stable bipolar spindle attachments, presumably due to the inability to differentiate functional kinetochore domains on individual sister chromatids. In the presence of this aberrant chromosome behavior a stable first meiotic spindle is not formed, the spindle poles continue to elongate, and the vast majority of cells never initiate anaphase. These results suggest that, in female meiotic systems in which spindle formation is based on the action of multiple microtubule organizing centers, the chromosomes not only promote microtubule polymerization and organization but their attachment to opposite spindle poles acts to stabilize the forming spindle poles.

MeSH Terms
Adaptor Proteins, Signal Transducing Anaphase/genetics,physiology Animals Carrier Proteins Centrosome/metabolism Chromosome Segregation/genetics,physiology Chromosomes/genetics,physiology Female Homozygote Kinetochores/physiology Male Meiosis/genetics,physiology Mice Mice, Knockout MutL Protein Homolog 1 Mutation Neoplasm Proteins/genetics,physiology Nuclear Proteins Oocytes/physiology Recombination, Genetic/genetics,physiology Sex Chromosomes/genetics,physiology Spindle Apparatus/physiology
Chemicals
Adaptor Proteins, Signal Transducing Carrier Proteins Mlh1 protein, mouse Neoplasm Proteins Nuclear Proteins MutL Protein Homolog 1
Authors & Affiliations
6 authors, click to expand affiliations / ORCID
Woods L M
Department of Genetics and Center for Human Genetics, Case Western Reserve University and University Hospitals of Cleveland, Cleveland, Ohio 44106, USA.
Hodges C A
Baart E
Baker S M
Liskay M
Hunt P A
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Article Info
Journal
The Journal of cell biology
Abbr.
J Cell Biol
ISSN
0021-9525
DOI
10.1083/jcb.145.7.1395
Published
1999-06-28
Pages
1395-406
Language
English
Region
United States
NLM ID
0375356
PMCID
PMC2133173
Subset
IM
Grants
NICHD NIH HHS · R01 HD31866 · United States
External Links
PubMed source DOI: 10.1083/jcb.145.7.1395 PMC Full Text View journal details
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