Biology Reference
In-Depth Information
4.4 Centrosome-Nuclear Interactions and Reprogramming
Abnormalities in Somatic Cell Nuclear Transfer Embryos
The tight structural connections of the centrosome with the nucleus are also
apparent in nuclear isolations in which the centrosome is typically co-isolated
along with the nucleus unless specific centrosome-nucleus separation methods are
employed. This close connection becomes important for SCNT embryos in which
an oocyte is enucleated and genomic material is replaced with a somatic cell
nucleus that also contributes the nucleus-associated centriole-centrosome com-
plex, thereby providing the centrosomal core structure that is normally contributed
by sperm during fertilization. Like the somatic cell nucleus, the somatic cell's
centriole-centrosome complex needs to be reprogrammed in SCNT to fulfill
functions that are normally carried out by the blended sperm-oocyte centrosomal
complex (reviewed in Schatten et al.
2009a
,
2009b
) which includes formation of
the mitotic apparatus during cell division. Reprogramming of the somatic cell's
centrosome complex depends on regulation by the enucleated oocyte to provide
components that are important for embryonic centrosome cell cycles. While
reconstructed SCNT eggs provide an ideal analysis system for centrosome regu-
lation very few studies have been performed so far on centrosome regulation in the
SCNT embryo system. However, studying the complexities between requirements
for embryonic cells compared to somatic cells may bring about further insights
into
centrosome
biology
and
correlations
between
nuclear-centrosome
interactions.
Live births resulting from SCNT reconstructed embryos have been obtained for
most animal species; however, in most cases the success rate is limited to 1-5 %
which indicates incompatibilities of the oocyte to reprogram the somatic cell
nucleus and its associated centrosomal complex. Indeed, our studies in porcine
SCNT reconstructed eggs revealed that 39.4 % of reconstructed eggs displayed
centrosomal abnormalities during the first cell cycle (Zhong et al.
2007
)as
determined by c-tubulin and/or centrin-2 and correlated microtubule staining
patterns. These centrosomal mitotic abnormalities may result in developmental
abnormalities or contribute to cellular pathologies that may be manifested as
adulthood diseases later in life. Reprogramming of somatic cell centrosomes
begins shortly after SCNT within the first embryonic cell cycle which spans ca.
24 h and is a very short time for centrosomal reprogramming considering that
somatic cell centrosomes are different from reproductive cell centrosomes, perhaps
containing different centrosomal compositions and different capabilities to perform
cell cycle-specific functions that are precisely provided by regulatory factors in the
somatic cell cytoplasm for somatic cell cycles; centrosome functions may require
different regulation in embryonic cells.
Centrosomal abnormalities may account for abnormal cell divisions during
different stages of development and may be part of the cellular incompatibilities
that allows only 1-5 % of reconstructed embryos to develop to full term resulting
in healthy offspring. Details and thoughts on the possible reasons underlying
