Wolbachia-induced CI results from a
delay of the male pronucleus to enter metaphase
Uninfected females are
unable to produce viable offspring with infected male flies.
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The ability of Wolbachia to rapidly spread through
an insect population results largely from a form of Wolbachia-induced male sterility
known as Cytoplasmic incompatibility (CI). Wolbachia-induced CI arises when an
infected male mates with an uninfected female. This cross results
in chromosome segregation defects in the first zygotic division and
embryonic lethality. However, if the infected male mates with
females infected with the same Wolbachia strain, no embryonic lethality
is observed (this is called rescue). Infected females have a
tremendous selective advantage over uninfected females because they can
successful mate with either infected or uninfected males.
Cytological analysis reveals that in incompatable (CI) crosses, the
paternal chromosomes do not condense and fail to segregate during the
first mitosis. In contrast, the maternal chromosomes condense and
segregate normally. CI crosses from mosquitos, flies, and wasps
all
exhibit these same defects, suggesting that Wolbachia may disrupt
conserved host targets.
In CI crosses,
paternal chromosomes condense later than the female chromosomes and
bridges form between segregating chromosomes during telophase.
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Based on
our studies of embryonic cell cycle checkpoints, we realized
that the condensation defects may be an indirect result of altering the
relative timing of the male and female pronuclei. Through
immunofluorescence assays that indicate CDK1 activity, we were able to
show that cell cycle progression of the male pronucleus is slowed
relative to the female pronucleus in CI crosses. In contrast,
uninfected crosses or crosses of infected males and infected females,
exhibit normal synchronous timing of the male and female
pronuclei. Our interpretation of these results was that CI
results from a significantly slowing of the male pronucleus relative to
the female pronucleus. In the rescue cross in which both parents
are infected with Wolbachia,
the cell cycle of both the male and female
pronuclei are equally slowed restoring synchrony. This work is
published in Science (Tram
et al. 2002).
Our model predicts that CI simply results from an asynchrony between
the male and female pronuclei and that the pronuclei are not
damaged. We genetically tested this prediction by determining
whether a paternal Wolbachia-modified
pronucleus can support
androgenetic development (from the paternal pronucleus only).
These experiments demonstrated that control crosses but not CI crosses
support androgenetic development arguing against pronuclear synchrony
as the primary cause of CI. The work and a related study was
recently published in Genetics (Ferree
and Sullivan
2006) and the Journal of Cell Science (Tram
et al.
2006). Based on these findings, our current working
hypothesis is
that CI results from asynchrony between the paternal pronucleus and the
cell cycle of the egg cytoplasm.
We have initiated a genetic
screen to identify dosage sensitive modifiers of CI. We are
excited about this approach because we have found that reducing the
maternal dosage of specific genes, dramatically reduces the strength of
CI. We are now pursuing the molecular and cellular basis of this
suppression.
Tram U, Fredrick K,
Werren
JH, Sullivan W. (2006) Paternal chromosome segregation
during the first mitotic division determines Wolbachia-induced cytoplasmic
incompatibility phenotype. J Cell Sci.
119: 3655-63
Ferree PM, Sullivan
W. (2006) A Genetic Test of the Role of the Maternal
Pronucleus in Wolbachia-Induced Cytoplasmic Incompatibility in
Drosophila melanogaster.
Genetics
173(2): 839-47.
Ferree, P.M., H.M.
Frydman, J.M. Li, J. Cao, E. Wieschaus, W. Sullivan. (2005)
Wolbachia utilize
host microtubules and dynein for anterior localization in the Drosophila oocyte. PLoS
Pathogens 2: 0111-0124.
Tram,
U., P. Ferree, and W. Sullivan.
(2003) Identification of Wolbachia-host
interacting factors through cytological analysis.
Microbes
Infect 5(11): 999-1011.
Tram,
U., and W. Sullivan (2002) Role of delayed nuclear envelope
breakdown and mitosis in Wolbachia-induced cytoplasmic
incompatibility. Science. 296:
1124-1126.
This material is based
upon work supported by the National Science
Foundation under Grant No. 0091265.
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