Biology Reference
In-Depth Information
While the Drosophila systemhas enormous potential for studies aimed at
a mechanistic understanding of PD, it is also important to point out that PD
modeling in Drosophila is still relatively new and that the reagents and meth-
odologies for conducting these studies are evolving. In particular, important
priorities of future work should be to define the most appropriate methods for
analyzing DA neuron integrity and to resolve conflicts in studies of some of the
current Drosophila models of PD. It is also imperative that we have realistic
expectations from these models. For example, at present the phenotypes of the
loss-of-function Drosophila models of PD do not precisely match the phenotypes
of humans with mutations in the corresponding genes. While these findings may
be of concern, phenotypic differences resulting from mutations in orthologous
genes in different species often belies significant underlying molecular pathway
conservation. Indeed, the weight of evidence suggests that the phenotypes asso-
ciated with the Drosophila
models, which include
sensitivity to oxidative stress agents and mitochondrial dysfunction, are directly
relevant to the mechanisms implicated in PD. Nevertheless, Drosophila are still a
relatively simple model organism, far less complex than humans, hence, it is
understandable that some aspects that may be relevant or even crucial to our
understanding of a particular human disease may not be evident inDrosophila. For
example, certain triplet repeat sequences underlying numerous neurological dis-
eases are known to expand during germline transmission, causing a more severe
syndrome in subsequent generations, but appear to be refractory to expansion in
Drosophila (Jackson
parkin
,
PINK1
, and
DJ-1
, 2005). However, to date we have only just begun to tap
the insight that modeling PD in Drosophila can potentially provide. I believe that
these advantages will be best realized if we focus our efforts on understanding what
the phenotypes of these models are telling us and take full advantage of the power
of genetics to lead us down unexpected, and even unintuitive, paths.
et al.
Acknowledgments
I wish to thank the members of my laboratory for their time, effort, and commitment to these
projects. I would also like to thank Leo Pallanck for his generous support in establishing my own
group and for continued stimulating discussions. The work in my lab is supported by grants from the
Wellcome Trust (WT081987 and the Neurodegeneration Disease Initiative WT089698), Parkin-
son's UK (G-0713), and the European Commission FP7 (241791). The MRC Centre for Develop-
mental and Biomedical Genetics is supported by Grant G070091.
References
Adams, M. D., Celniker, S. E., Holt, R. A., Evans, C. A., Gocayne, J. D., Amanatides, P. G.,
Scherer, S. E., Li, P. W., Hoskins, R. A., Galle, R. F.,
et al
. (2000). The genome sequence of
Science 287, 2185-2195.
Andrews, H. K., Zhang, Y. Q., Trotta, N., and Broadie, K. (2002). Drosophila sec10 is required for
hormone secretion but not general exocytosis or neurotransmission.
Drosophila melanogaster
.
Traffic 3, 906-921.
