Biology Reference
In-Depth Information
mutant flies are unable to perform many basic adult behaviors, including
walking, climbing, and flying, indicating that these miRNAs ensure the
proper formation of internal adult structures during metamorphosis. 20E-
receptor regulated expression of
let-7-C
is critical because a
let-7-C
rescuing
transgene in which the 20E-receptor binding sites are missing is unable to
rescue the adult behavioral defects (
Chawla & Sokol, 2012
). As summarized
below, recent evidence indicates that
Drosophila let-7-C
miRNAs control
temporal cell fate decisions during developmental transitions and suggests
that defects in steroid hormone regulated temporal cell fate transitions lead
to the behavioral phenotypes displayed by
let-7-C
mutant flies.
The temporal wave of
let-7-C
expression during the larval-to-pupal tran-
sition plays important roles in ensuring the cells adopt appropriate stage spe-
cific behaviors and morphologies. For example, genetic elimination of
let-7
and
miR-125
leads to a delay in cell-cycle exit in the pupal wing disc, where
cells usually stop dividing early in metamorphosis (
Caygill & Johnston,
2008
). Thus, mutant adult wings contain more cells than control flies,
although the relevant target in this case remains unknown.
In addition,
let-7-C
miRNAs ensure that both centrally locatedmushroom
body (MB) neurons as well as peripherally located motoneurons adopt appro-
priate stage-specific morphologies by regulating a pair of
bric-a-brac/tramtrack/
broad-complex
(BTB)-domain containing zinc finger (BTB-ZF) transcription
factors. In the MBs,
let-7-C
miRNAs synchronize cell fate transitions amongst
a set of eight neuronal linages by downregulating the BTB-ZF
chronologically
inappropriate morphogenesis
(
chinmo
)(
Wu, Chen, Mercer, & Sokol, 2012
). The
adult fly brain contains two MBs, which are composed of four distinct neu-
ronal subtypes (
g
,
a
0
/
b
0
, pioneer
a
/
b
,and
a
/
b
neurons) that are generated by
eight neural progenitor cells (
Ito & Awasaki, 2008; Lee, Lee, & Luo, 1999;
Zhu et al., 2006
). These progenitors generate the
g
,
a
0
/
b
0
,pioneer
a
/
b
,
and
a
/
b
subtypes sequentially during development, so that
g
neurons are born
during early larval stages while the
a
0
/
b
0
,pioneer
a
/
b
,and
a
/
b
neurons are
born at progressively later timepoints during the larval-to-pupal transition,
respectively (reviewed in
Lin & Lee, 2012
). Although many genes are
expressed in the MB and have effects on MB morphology, Chinmo is unique
because its expression is gradually downregulated as transitions between
g
,
a
0
/
b
0
,pioneer
a
/
b
,and
a
/
b
production occur suggesting a mechanism for the
ordered production of neuronal subtypes (
Zhu et al., 2006
). Indeed, genetic
analysis indicates that
chinmo
has a dosage sensitive effect on MB cell fate, and
that its post-transcriptional downregulation during the larval-to-pupal transi-
tion is responsible for the
g!a
0
/
b
0
!
pioneer
a
/
b!a
/
b
cell fate transitions
