Biology Reference
In-Depth Information
normal fertilization (Liu et al.
2006
; Alvarez-Sedó et al.
2011
; Schatten et al.
2012
).
Detailed studies on NuMA before and after fertilization will be important to
determine whether NuMA dysfunctions play a role in male-factor infertility,
embryo abnormalities, and whether NuMA dysfunctions at this early stage of an
embryo's development will result in adulthood diseases, as misregulation of
NuMA can result in the formation of multipolar mitoses which are hallmark
features for cancer development and progression (Kammerer et al.
2005
; reviewed
in Sun and Schatten
2006
). In this context it is also worth noting that NuMA
becomes extensively modified after herpes simplex virus (HSV) infection which
induces solubilization and relocalization of NuMA (Yamauchi et al.
2008
); it may
affect subsequent NuMA dynamics that may play a role in mitotic abnormalities
underlying diseases such as cancer.
Close attachment between the centrosome and the nucleus is important for
coordinated pronuclear migration and apposition of male and female pronuclei and
formation of the zygote aster that evolves into the mitotic apparatus to separate the
parental genomes equally to the dividing daughter cells (reviewed in Schatten and
Sun
2009a
,
2009b
,
2010
,
2011a
,
2011c
). The structural associations of centro-
somes with the nucleus have been described in somatic cells (Meyer et al.
2011
)
and studies in C. elegans have explored the mechanisms of centrosome-nuclear
relationships but only sparse information is available on such structural and
functional relationships in mammalian embryo cells. In C. elegans, ZYG-12,
SUN-1, and LIS-1 interact with dynein to contribute to the attachment of cen-
trosomes to the nucleus in early development and it was proposed that recruitment
of dynein to the cytoplasmic surface of the nuclear envelope is critical for the
attachment of centrosomes (Malone et al.
2003
; Meyerzon et al.
2009
); two genes,
zyg-12, and sun-1 were shown to be essential for centrosome attachment and
embryonic development in this system (Fridkin et al.
2004
; Malone et al.
2003
). It
was further proposed that the inner nuclear membrane and nuclear lamina proteins
are involved in centrosome-nucleus attachment (Askjaer et al.
2002
; Galy et al.
2006
). In C. elegans, Meyerzon et al. (
2009
) described a novel role for nuclear
lamina proteins in centrosome attachment to the nuclear envelope. The mecha-
nisms described for nuclear-centrosomal attachment in C. elegans have been
explored for the first few cell divisions in early embryogenesis but may be different
during later development, as ZYG-12 is not required for later stages of embryo-
genesis. These studies in C. elegans provide important steps toward understanding
embryonic centrosome-nuclear attachment mechanisms while we still know only
little about such molecular mechanisms for mammalian embryos.
In fibroblast cells, it was shown that lamin and the integral inner nuclear
membrane protein emerin are involved in centrosome attachment, as fibroblasts
from emerin-defective human patients or lamin A/C mutant mice displayed cen-
trosome detachment phenotypes (Lee et al.
2007
; Salpingidou et al.
2007
). Emerin
is present at both the inner and outer nuclear membrane and it was determined that
emerin interacts with tubulin which led to the proposed model that emerin on the
