Following ncc-1 RNAi treatment, fertilized oocytes
fail to complete meiotic
maturation. At the time of injection, a large number of germ precursor cells
are in pachytene of meiosis I. These nuclei progress through meiotic
prophase I but do not initiate metaphase, indicating that ncc-1 is required
to promote the transition from prophase to metaphase in meiosis. A role in
meiosis is consistent with the function of Cdk1/Cdc2 in other eukaryotes. In
fact, Xenopus p34cdc2 was discovered by the biochemical characterization of
maturation promoting factor (MPF), a cytoplasmic factor that induces meiotic
maturation when injected into immature oocytes. Completion of meiosis I and
II is a two step process in amphibians. Progesterone, or injection of MPF,
triggers oocytes that are arrested in diplotene of prophase I to progress
through meiosis I. Mature oocytes will subsequently arrest in metaphase of
meiosis II and can be triggered by fertilization to complete meiosis.
Meiotic maturation in C. elegans is induced by a factor in sperm that is
independent from the sperms function at fertilization. In the absence
of
sperm, C. elegans oocytes arrest for prolonged periods in diakinesis. Future
studies may reveal whether progesterone and the sperm factor activate
similar pathways that induce p34cdc2 and ncc-1, respectively, and trigger
progression to meiotic metaphase I (Boxem, 1999 and references).
Does progression through meiotic prophase require
ncc-1 function? In the
RNA-injected animals, oocyte development appears normal and chromosomes
become fully condensed. It cannot be exclude that inactivation of ncc-1 by
RNAi is incomplete. However, several observations support effective
inactivation. If inactivation was complete, entry into meiotic development,
meiotic prophase progression, condensation of chromosomes to diakinesis
bivalents and oocyte development can all occur independent of ncc-1. If
these processes do require ncc-1 activity, this must be less activity than
required for germ cell proliferation and for the transition from diakinesis
to meiosis I. As yet, formation of diakinesis bivalents of normal morphology
in the absence of Cdk1 activity has not been described in any eukaryote.
During spermatogenesis in Drosophila, DNA condensation can occur in the
apparent absence of Dmcdc2 activity. However, male meiosis in Drosophila
does not involve meiotic recombination and attachment of bivalents by
chiasmata. Nuclear envelope breakdown occurs slowly in mature ncc-1( RNAi)
oocytes; by the time it is accomplished, meiosis would normally have been
completed. The fact that degradation still occurs could indicate incomplete
inactivation of ncc-1, as Cdk1 is believed to phosphorylate nuclear lamins
and to trigger nuclear envelope breakdown in mitosis. However, other kinases
have also been implicated in nuclear lamin phosphorylation, including S6
kinase II and protein kinase C. Such kinases may trigger nuclear envelope
breakdown in the absence of ncc-1 activity (Boxem, 1999).