Gene-Centered Regulatory Network Mapping - Caenorhabditis Elegans: Molecular Genetics and Development - page 280

interaction. For instance, assays that are performed with mixed populations of
animals can easily miss interactions that occur only in a few cells or only during a
short developmental time. Indeed, in our study of the B0507.1 promoter, we found a
reduction in expression upon loss of the TF CES-1 only in the spermatheca, rectal
gland, and pharyngeal-intestinal valve and, since these are not large tissues, this
would be extremely difficult to detect in mixed population whole animal assays such
as qPCR ( Reece-Hoyes et al., 2009 ).
V. Future Challenges
The comprehensive mapping of gene regulatory networks in C. elegans has only
just started. Future studies are needed to complete transcriptional networks by high-
throughput Y1H assays, and by other complementary assays such as ChIP. In addi-
tion, it will be highly useful to systematically generate promoter::GFP constructs and
corresponding transgenic C. elegans lines for all worm genes. Such lines can then be
used to examine promoter activity under different experimental or physiological
conditions and to validate transcriptional networks, for instance using TF mutants or
TF knockdown. Further, the continued experimental analysis of microRNAs and
other small RNAs will be of extremely high value. Experimental methods also need
to be developed and applied to assess other regulatory networks, such as those
involving RNA binding proteins, signaling molecules, and metabolites. Finally, it
will be exciting to go beyond static network models that represent a compilation of
the interactions that can occur in the animal and to incorporate the dynamics and
levels of gene and regulator expression and activation throughout the lifetime of the
nematode.
Acknowledgments
I thank members of my lab for their hard work and especially John Reece-Hoyes and Lesley MacNeil
for critical reading of the manuscript. Work in my lab is supported by the National Institutes of Health
(DK068429 and GM082971) and by the Ellison Medical Research Foundation.
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