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In-Depth Information
Altogether, this collection of studies of the bantam sensor helped reveal
an extraordinary diversity of transcriptional inputs into this miRNA. Such
complexity befits an essential growth locus such as bantam, presumably to
coordinate precise tissue growth underlying appropriate development.
Interestingly, bantam has additional roles independent of growth, such as
in scaling growth of neural dendrites (
Parrish
et al
., 2009
), maintenance of
germline stem cells (
Yang
et al
., 2009
), and control of circadian rhythm
(
Kadener
et al
., 2009a
). Presumably each of these other settings is associated
with other transcriptional inputs to bantam, which remain to be elucidated.
Finally, while the bantam sensor is the most well studied in
Drosophila
, other
sensors for individual miRNAs [e.g., miR-9a (
Bejarano
et al
., 2010
)or
miR-14 (
Varghese
et al
., 2010
)] or for miRNA-regulated 3
0
UTRs
(
Fig. 8.4
B;
Bejarano
et al
., 2010
;
Brennecke
et al
., 2003
;
Friggi-Grelin
et al
., 2008
) have been informative probes of miRNA activity
in vivo
.In
many postembryonic tissues, one can induce clones that are homozygous
for a mutant allele of interest. In combination with a miRNA sensor,
induction of clones of a miRNA mutant can report on the activity of that
miRNA in a particular tissue; derepression of a miRNA or 3
0
UTR sensor
reports directly on miRNA activity (
Fig. 8.4
C).
6. Conclusions and Future Prospects
We have emphasized a broad selection of
Drosophila
genetic techni-
ques used to manipulate miRNA activity, elucidate associated pathways and
key target genes, and interrogate miRNA expression, all in the context of
the intact animal. Overall, we wish to highlight that miRNAs are just like
any other genes, in that they can be studied using most of the same
techniques used to study “interesting” protein-coding genes. Although
the field of miRNA biology is dominated by reverse genetics, many
miRNAs are associated with palpable phenotypes, both loss- and gain-of-
function. However, it can take some searching to find the right place, the
right time, and the right markers with which to characterize miRNA
activities. However, we also highlight that manifestations of miRNA dys-
function have existed in
Drosophila
, as with
C. elegans
, long before the
formal recognition of miRNAs as a unified class of regulatory molecule.
We conclude with a few final points with a view to the future of miRNA
genetics in
Drosophila
.
First, we are struck by the fact that overexpression of so many miRNAs
induces compelling and interpretable phenotypes. This is not necessarily
expected from the viewpoint that animal miRNAs predominantly mediate
subtle repression of large groups of transcripts, which might imply that
manipulation of miRNAs might either yield few phenotypes or
