Recent progress in understanding the role of ecdysteroids in adult insects: Germline development and circadian clock in the fruit fly Drosophila melanogaster

Abstract

Steroid hormones are one of the major bioactive molecules responsible for the coordinated regulation of biological processes in multicellular organisms. In insects, the principal steroid hormones are ecdysteroids, including 20-hydroxyecdysone. A great deal of research has investigated the roles played by ecdysteroids during insect development, especially the regulatory role in inducing molting and metamorphosis. However, little attention has been paid to the roles of these hormones in post-developmental processes, despite their undisputed presence in the adult insect body. Recently, molecular genetics of the fruit fly Drosophila melanogaster has revealed that ecdysteroid biosynthesis and signaling are indeed active in adult insects, and involved in diverse processes, including oogenesis, stress resistance, longevity, and neuronal activity. In this review, we focus on very recent progress in the understanding of two adult biological events that require ecdysteroid biosynthesis and/or signaling in Drosophila at the molecular level: germline development and the circadian clock.

Keywords: Circadian clock; Ecdysone; Germline stem cell; Insect; Oogenesis; Steroid hormone.

Fig. 1

Schematic representation of ovariole and germarium in Drosophila melanogaster. a The Drosophila ovary is composed of 15–20 ovarioles. The continuous developing egg chamber is divided into 14 stages. Each egg chamber is composed of an oocyte, nurse cells and somatic follicle cells. Vitellogenesis occurs after stage 8 egg chamber. b The germarium resides in the tip of the ovariole. Germline stem cells (blue) are maintained by somatic niche cells comprising the terminal filament, cap cells, and escort stem cells (green). Germline stem cells produce another stem cell by self-renewal and also divide asymmetrically to produce daughter cells called cystoblasts (red). The cystoblast divides four times with incomplete cytokinesis to form 15 nurse cells and one oocyte in each egg chamber, which are enveloped by follicle cells (gray). Illustration in the egg chamber shows proliferation and differentiation of cystoblasts from the 2-(left) to 16-cell stage. GSCs and cystoblasts can be identified by the morphology of the spectrosome, a germline-specific membranous organelle (yellow). Developing cystocytes contain the fusome, a derivative of the spectrosome that shows more branched morphology (yellow)

Fig. 2

Different roles of ecdysteroids in regulating progression of oogenesis. Ecdysteroid biosynthesized in the stage 10 follicle cells regulates many aspects of oogenesis to function in the early and mid-stage of the egg chamber. Stage 8 checkpoint is determined by nutritional status and regulated by E75A and E75B. Starvation leads to apoptosis of the egg chamber via E75A, whose expression is negatively regulated by E75B under feeding conditions Ecdysteroid signaling in the CNS mediates lipid accumulation at stage 10 egg chamber via SREBP and LpR2. Ecdysteroids also function in early oogenesis at the germarium such as niche cell formation, follicle cell formation, GSC maintenance and cyst cell differentiation. EcR/USP are expressed in the somatic niche cells or GSCs to control different ecdysone responsive genes. While E74 controls GSC proliferation, E75 affects 16-cell cyst differentiation. Broad and E78 regulate niche cell formation during ovarian development in late larval stages

Fig. 3

Scheme illustrating ecdysone signaling factors in the molecular machinery of the Drosophila circadian clock. The figure is modified from Itoh and Matsumoto [92]. The signal of 20-hydroxyecdysone (20E), the most biologically active ecdysteroid, is transduced primarily through the action of the specific receptor for 20E. This receptor is a heterodimer of Ecdysone receptor (EcR) and Ultraspiracle (Usp), which binds a specific DNA element when 20E is present. The 20E-bound form of EcR/Usp complex activates transcriptions of vrille (vri) and Early gene at 23 (E23). The CLK-CYC also activates transcriptions of period (per), vri and E23. The E23 protein specifically negates the 20E response. Furthermore, this EcR-Usp complex starts the ecdysteroid cascade with the expression of E75. The E75 and UNF activate transcriptions of per