MicroRNA function in Drosophila melanogaster

Abstract

Over the last decade, microRNAs have emerged as critical regulators in the expression and function of animal genomes. This review article discusses the relationship between microRNA-mediated regulation and the biology of the fruit fly Drosophila melanogaster. We focus on the roles that microRNAs play in tissue growth, germ cell development, hormone action, and the development and activity of the central nervous system. We also discuss the ways in which microRNAs affect robustness. Many gene regulatory networks are robust; they are relatively insensitive to the precise values of reaction constants and concentrations of molecules acting within the networks. MicroRNAs involved in robustness appear to be nonessential under uniform conditions used in conventional laboratory experiments. However, the robust functions of microRNAs can be revealed when environmental or genetic variation otherwise has an impact on developmental outcomes.

Keywords: Drosophila; MiRNAs; MicroRNAs.

Figure 1. Control of tissue growth by miRNAs

(A) Regulated bantam expression by the Hippo and TGF pathways. Signals are transduced via the Hippo (Hpo) and Wts kinases, aided by cofactors Sav and Mats, respectively. This effectively blocks Yorkie (Yki) from entering the nucleus and activating bantam transcription. Transcription also requires either Homothorax (Hth) or Mad. Dachshund (Dach) blocks this in the eye. (B) Cross-talk between the Hippo and EGFR pathways mediated by bantam and Capicua. (C) Regulation of growth through the Hedgehog (Hh) pathway is mediated by several miRNAs. Ihog and Boi enable productive interaction between Hh and its receptor Patched (Ptc).

Figure 2. Cross-talk via miRNAs between various growth hormone pathways

Feedback occurs between insulin producing cells (IPCs), the prothoracic gand (PG), and the fat body (FB). ILPs, ecdysone, and Imp-L2 mediate these interactions. Within each secretory gland, miRNAs directly target various genes including Sugarbabe and U-shaped (Ush). The identities of other direct targets is less understood.

Figure 3. Control of developmental variation by miRNA miR-9a

(A) Natural genetic variation in a population of flies can lead to above-average transcription of the senseless gene. Nevertheless, Senseless protein output is rendered uniform by miR-9a repression. This results in less variation in bristle number. (B) Natural genetic variation can also lead to below-average senseless transcription. miR-9a is unable to render Senseless protein output to a normal level, and flies can exhibit a below-average bristle number. (C) Raising flies at different temperatures has little effect on bristle number phenotypes because miR-9a represses Senseless protein output.