MicroRNAs as Components of Systemic Signaling Pathways in Drosophila melanogaster - Current Topics in Developmental Biology - page 104

Figure 4.2 Drosophila miRNAs in the Ecdysone and JH pathways. The 20-
hydroxyEcdysone (20E) steroid hormone regulates target genes via its receptor, a
heterodimer composed of EcR and Usp. Direct targets of the 20E receptor include tran-
scription factors Eip74ef, Eip75b, and broad as well as the let-7-C miRNA locus ( Chawla &
Sokol, 2012 ). These let-7-C miRNAs (miR-100, let-7, and miR-125) in turn repress the
expression of abrupt, chinmo, dp, and imp to control neuronal fate, morphology, and
maintenance as well as germline stem cell number ( Caygill & Johnston, 2008; Gehrke
et al., 2010; Toledano et al., 2012; Wu et al., 2012 ). While activating let-7-C miRNAs,
20E represses three additional miRNAs, miR-8, miR-14, and miR-34 ( Jin et al., 2012;
Sempere et al., 2003; Varghese & Cohen, 2007 ). The regulation of miR-8 is via the
EcR/Usp targets 74ef and Broad ( Jin et al., 2012 ). miR-8 regulates Ush to control body
size, while miR-14 feeds back to regulate EcR to modulate 20E signaling ( Jin et al.,
2012; Varghese & Cohen, 2007 ). miR-34 is also activated by JH and prevents neu-
rodegeneration in the adult brain by repressing Eip74ef ( Liu et al., 2012; Sempere
et al., 2003 ).

of this release is determined by a complex interplay between neuropeptide and
IIS signaling pathways and occurs in response to environmental cues like nutri-
tion availability. Circulating Ecdysone is converted to 20E in peripheral tissues,
and the active hormone then binds to a nuclear hormone receptor. This recep-
tor in an obligate heterodimer composed of two subunits, EcR and
ultraspiracle (Usp). A 20E-bound form of this receptor directly regulates the
transcription of target genes, triggering changes in gene expression that lead
to the whole-scale transformation of

the larvae into the adult during

metamorphosis.