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(
Zhu et al., 2006
). A mechanism for this post-transcriptional regulation was
suggested by a previously unannotated
chinmo
3'UTR that contains mul-
tiple binding sites for both
let-7
and
miR-125,
since
let-7-C
onset coincides
with Chinmo offset and the
a
0
/
b
0
!
pioneer
a
/
b!a
/
b
cell fate transitions
(
Wu et al., 2012
). These transitions are delayed in
let-7-C
mutants, leading to
an increase in the number of pioneer
a
/
b
neurons. Elevated Chinmo is
indeed responsible for the
let-7-C
mutant phenotype, since this increase
in pioneer
a
/
b
neurons is suppressed by genetic reduction of
chinmo
levels.
let-7-C
miRNAs likely control Chinmo levels directly; Chinmo expression
is eliminated in MBs of early larvae when
let-7-C
miRNAs are prematurely
expressed, Chinmo expression inappropriately persists in
let-7-C
mutant
pupae and adults, and the predicted
let-7
and
miR-125
sites in the
chinmo
3'UTRmediate reporter repression in cultured cells. Other as yet unknown
factors must also be responsible for the regulation of Chinmo expression
since cell fate transitions and Chinmo downregulation are delayed but
not eliminated in
let-7-C
mutants. Nevertheless, activation of
let-7-C
miRNAs during the larval-to-pupal transition shapes a temporal gradient
of Chinmo in order to specify cell fates of a mulitpotent neuronal lineage
over time.
Ecdysone is very likely involved in the activation of
let-7-C
miRNAs in
the MB, where
let-7-C
miRNAs apparently also regulate the expression of a
second BTB-ZF Abrupt to control MBmorphology.
let-7
expression is gen-
erally dependent on Ecdysone in the adult brain, since the miRNA is vir-
tually eliminated in
ecd
mutants (
Kucherenko, Barth, Fiala, & Shcherbata,
2012
). However,
let-7-C
control of temporal identity in the MB appears
to be partially independent of the 20E-receptor, since the normal number
of pioneer
a
/
b
neurons is found in
let-7-C
mutant adults that harbor a res-
cuing transgene devoid of known 20E-receptor binding sites (Yen-chi Wu
and Nick Sokol, unpublished observations). Genetic depletion experiments
indicate that the 20E-receptor plays important roles in controlling the rem-
odeling and final morphology of
g
and
a
/
b
lobes (
Kucherenko et al., 2012;
Lin, Huang, & Lee, 2009
). Part of this function may be mediated by
let-7
regulation of the previously known
let-7
-specific target Abrupt, since
genetic depletion of
abrupt
rescues a
let-7
dependent defect in
a
/
b
lobe mor-
phology (
Burgler & Macdonald, 2005; Kucherenko et al., 2012
).
let-7-
C regulation of
abrupt
also ensures that post-mitotic motoneurons
adopt their appropriate developmental stage-specific morphologies.
let-7-C
mutants exhibit persistence into adulthood of pupal muscles and their
corresponding innervations, and a failure to fully develop certain adult
