Interplay Between Spindle Architecture and Function - International Review of Cell and Molecular Biology - page 117

However, direct imaging of spindle organization through electron micros-
copy remains the gold standard for determining spindle architecture. Studies
of various small fungal spindles through electron tomography have establish
the groundwork for larger, more complex spindle structures and provided an
important structural context for studies in those systems, as well as insight
into general principles of spindle architecture and evolution. Even recon-
structions or EM images of relatively small slices of larger complex spindles
will provide important constraints on MT length distributions and spatial
organization that could be incorporated into studies of MT dynamics
and simulations.
6. CONCLUSIONS
By altering the basic spindle plan, cells have evolved mechanisms that
promote robust chromosome segregation and cell division that accommo-
dates their diverse morphologies and functions. Given the critical role of the
spindle, it is not surprising that many associated factors have been linked to
diseases in which chromosome segregation is disrupted ( Noatynska et al.,
2012 ). For example, a significant percentage of MAPs that affect spindle
assembly or function have altered expression levels at the mRNA or protein
level in a variety of cancers ( Bieche et al., 2011; Chang et al., 2012; Wang
et al., 2010 ). Chromosome segregation errors in female meiosis also pose a
significant problem and lead to the high incidence of human miscarriage and
developmental diseases such as Down syndrome (trisomy 21; Hassold and
Hunt, 2001 ). The unique architecture of the meiotic spindle, which must
maintain its structure and function for long periods in oocytes prior to fer-
tilization, provides an interesting example of the role and effects of spindle
structure and the importance of understanding the underlying mechanisms.
We are now approaching a more mechanistic understanding of how
spindle architectures are established. Work from a variety of model systems
continues to fill gaps in our current knowledge and importantly provides the
basis for comparative analysis that allows the identification of general prin-
ciples and specific elaborations of the spindle plan. Specifically, insights into
the biology of the spindle matrix have been gleaned from studies in Drosoph-
ila. The complete MT structure of spindles in fungi by electron tomography
have provided high-resolution views of spindle architectures and are poised
to leverage this information in combination with the vast amounts of geno-
mic data now available. Xenopus extract systems have been particularly useful
for studying female meiotic spindle architecture and mechanisms that