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J. Cell Biol.,
Volume 145, Number 7, June 28, 1999 1395-1406
* Department of Genetics and Center for Human Genetics, Case Western Reserve University and University Hospitals of
Cleveland, Cleveland, Ohio 44106; 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.
Department of Animal Breeding, Wageningen Agricultural University, Wageningen 6709 PG, The Netherlands; § Division of Nutritional Sciences and Toxicology, University of California, Berkeley, Berkeley, California
94720; and Department of Molecular and Medical Genetics, Oregon Health Sciences University, Portland, Oregon 97201
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