Biology Reference
In-Depth Information
muscles and their respective innervations (
Caygill & Johnston, 2008; Sokol
et al., 2008
). Genetic depletion of
abrupt
suppresses the
let-7
mutant pheno-
type, indicating that ectopic Abrupt contributes to the
let-7
phenotype
(
Caygill & Johnston, 2008
). The finding that
let-7-C
adults display both per-
sistent juvenile and immature adult characteristics indicates that the essential
function of
let-7-C
as a regulator of developmental timing appears to be
evolutionarily conserved from worms to flies, and provides a cellular basis
for the behavioral defects displayed by
let-7-C
adults.
let-7-C
miRNAs have also been found to regulate dopaminergic neuron
and GSC behavior in adults, although it remains unclear whether hormonal
control of
let-7-C
is important for these post-developmental functions.
let-7
mutants adults, for example, have a reduced number of dopaminergic neu-
rons (
Gehrke, Imai, Sokol, & Lu, 2010
). This phenotype may indicate a role
for
let-7
in maintaining this post-mitotic neuron subtype, since injection of
let-7
antisense RNA into the adult leads to a similar phenotype.
let-7
appears
to mediate this role by repressing translation of the
dp transcription factor
(
dp
),
since Dp expression is elevated in
let-7
mutants and expression of a
let-7
insensitive transgene also leads to dopaminergic neuron loss.
let-7
has
been implicated in the age-dependent loss of GSCs in males (
Toledano,
D'Alterio, Czech, Levine, & Jones, 2012
). The number of GSCs is con-
trolled in part by their rate of self-renewal, which is modulated by the janus
kinase/signal transducer and activator of transcription (JAK-STAT) path-
way.
let-7
can indirectly affect the expression of the secreted activating ligand
of this pathway by directly controlling the levels of the RNA-binding pro-
tein Igf-II mRNA-binding protein (Imp). Overexpression of
let-7
in the
hub cells that surround the GSCs can repress Imp via a binding site in the
imp
3'UTR, leading to a reduction in GSC number. Thus, an observed
increase of
let-7
expression in the hub cells during adulthood could be
responsible for the age-dependent loss of GSCs by regulating the JAK-
STAT pathway.
4.5. miR-14 and miR-8: molecular links between steroid
and insulin signaling pathways
Coordination between the 20E and insulin signaling pathways regulates the
rate of growth during development, and may also function post-developmen-
tally to link nutritional status with adult processes like reproduction, behavior,
and stress resistance (
Schwedes & Carney, 2012; Tennessen & Thummel,
2011
). Both
miR-14
and
miR-8
represent molecular connections between
these pathways, since they are repressed by 20E and, in turn, repress genes
