Biology Reference
In-Depth Information
strategies, involving genetics, cell biology, biochemistry, and functional genomics, to
gain a more complete understanding of how gene regulatory networks control a
particular biological process. The aim of this review is to provide an overview of the
approaches available to identify and construct the genetic pathways using C. elegans.
I. Introduction
C. elegans has emerged as a powerful model system for identifying the genes and
genetic pathways that regulate a diverse array of fundamental biological processes.
The strengths of C. elegans include its invariant cell lineage, simplified cellular
landscape, transparency, short life cycle, and hermaphroditic reproduction, which
favor rapid genetic analysis. Complementing these traditional attributes, more recent
functional genomic technologies, including genome-scale transcriptional and phe-
notypic profiling as well as physical interaction mapping, have led to more instru-
ments in the C. elegans researcher
'
s tool box to uncover the genetic networks that
control developmental, behavioral, cell biological, and physiological processes.
Highlighting the utility of C. elegans is the leading role that this model system
has played in elucidating the genetic pathways regulating key biological processes
such as cell-fate specification (
Greenwald et al., 1983; Sternberg, 2004; Sternberg
and Horvitz, 1986
), apoptosis (
Kimble and Hirsh, 1979; Metzstein et al., 1998;
Sulston et al., 1983; Sulston and Horvitz, 1977
), RNA interference (RNAi)
(
Fire et al., 1998
), microRNA biology (
Reinhart et al., 2000; Simon et al., 2008
),
axon guidance (
Chan et al., 1996; Hao et al., 2001; Walthall and Chalfie, 1988
), cell
polarity (
Goldstein and Hird, 1996; Kemphues et al., 1988
), and aging (
Friedman
and Johnson, 1988; Kimura et al., 1997
).
The goal of this review is to provide a comprehensive overview of the approaches
available to C. elegans researchers to identify and construct the genetic pathways that
control biological events. Often these start with a simple genetic screen to identify
the key nonredundant genes that regulate a process of interest. Alternatively,
researchers sometimes stumble into a biological process when conducting reverse
genetics - knocking out or reducing the function of a gene of interest (often disease-
related) and studying the resulting phenotype. Once key genes are identified, reverse
genetics and sensitized screening approaches can be used to better focus and identify
redundant or modulatory genes. These approaches can often be complemented with
functional genomic and systems-level studies to gain a more complete understanding
of genetic pathways and the networks that guide these processes. In this review, we
first discuss representative designs underlying diverse genetic screens in C. elegans
with a uniform aim of identifying genes involved in a biological process of interest.
We then discuss new techniques being utilized to discover candidate genes, including
functional genomic techniques and their integration into systems-level analysis. This
is followed by an outline of strategies for constructing pathways with genes identi-
fied. Throughout we provide specific examples of screening and genetic pathway
construction to illustrate how these techniques are implemented.
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