Biology Reference
In-Depth Information
morphology, small size, near-invariant lineage and trans-
parency, together with the wealth of known mutant pheno-
types, make the worm an ideal test case for the development
of automated images, and thus we believe that improve-
ments in automated imaging in the worm will be an area of
progress that will have an impact well beyond the worm
field.
Thirdly, we believe that research into the mind of the
worm
events of early embryogenesis have been studied in a wide
variety of nematodes, showing the dizzying number of
ways in which a near-identical four-cell embryo can be
derived
[211]
. Many of the earliest analyses of embryo-
genesis in any nematode were undertaken in other nema-
todes such as Ascaris
[212]
and, while C. elegans has
clearly outpaced research on these other worms, it will be
intriguing to see how the re-application of new tools and
technologies, together with full genomic sequences, can
open up these fields. The approaches pioneered in C. ele-
gans are likely to be key also in the medically vital studies
of various pathogenic nematodes. Many of these, whether
plant pathogens or animal pathogens, are competent for
RNAi, and this is likely to identify key potential drug
targets and pathways. Together, the systematic examination
of the genetics of development in a wide range of related
nematodes is likely to shed key light on the constraints and
mechanisms of evolution, and this will be an intriguing area
to follow.
Since Sydney Brenner's first concerted drive to estab-
lish C. elegans as a simple animal model to understand the
genetic basis for development and the function of the
neuromuscular system, giant strides have been taken.
However, the simplicity of the biology of the worm and the
awesome power of worm genetics will continue to shed
light on central problems in genetics and animal biology in
the coming decades as new technologies and new
approaches open up untouched areas.
how information, in the form of electrical and
chemical signals, flows through the neuromuscular system
and integrates multiple inputs and stimuli
e
into robust
behavioral outcomes
is about to be transformed by
a number of technologies. The physical map of the
connections between all neurons and between neurons and
muscle cells is in some way analogous to the genome. The
genome encodes a huge number of possible cellular states,
and the precise sets of genes turned on and off determine
a large part of the functional state of the cell. Similarly, the
nervous system map shows the possible ways in which
information could flow and, while laser ablations show key
requirements for specific neurons, cross-talk and feedback
can complicate the interpretation of these results
e
visu-
alizing the actual temporal and spatial flow of information
from stimulus to response is the crucial missing piece to
understanding the worm brain. Great advances in imaging
and fluorescent reporters, together with advances in
microfluidics (e.g., in accurately controlling the worm
microenvironment
[203]
), mean it is now possible to carry
out real-time imaging of neurons firing in vivo (e.g., in
[204
e
207]
). Using the genetic toolbox available to study
the nervous system
e
large mutant collections that have
perturbed neuronal lineages, multiple cell-specific fluores-
cent markers etc.
e
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together with the guiding map of the
physical map of the nervous system of the worm, real-time
imaging will yield key insights into how information is
processed by an intact and complete animal brain.
Finally, we also anticipate an ever-deepening analysis
of other related nematodes. C. briggsae was Sydney
Brenner's first identified worm to 'tame', and comparisons
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[208]
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