Juvenile hormone molecular actions and interactions during development of Drosophila melanogaster

This review summarizes our understanding of the molecular mechanism of juvenile hormone (JH) action in the fruit fly, Drosophila melanogaster. It details the growing evidence that JH acts primarily at the level of gene expression and does so in apparently two different ways-directly, as a transcriptional regulator of JH "target genes," and indirectly, as a suppressor of 20-hydroxyecdysone (20E)-dependent transcriptional regulation. Since Drosophila has emerged as a model genetic system for the analysis of insect hormone action, particular emphasis in this chapter is placed on the analysis of mutants that have proved useful for acquiring understanding of insect hormone action during development and reproduction. During its life cycle, Drosophila melanogaster progresses through four structurally and functionally distinct stages-the embryo, larva, pupa, and adult. During embryogenesis, both maternal and zygotic gene expression contribute to the creation of the insect body plan; first establishing polarity, then segmentation, and finally, segment identity (Lawrence, 1992). After hatching, a sequence of three larval stages, or instars, occurs as the insect feeds and grows. Larvae are well adapted for feeding, being primarily composed of a tubular digestive system and an extensively anastomosing fat body whose function is analogous to the mammalian liver. Because insects, like all Arthropods, possess an external and rigid chitinous exoskeleton (the cuticle), larval growth is restricted and must be accompanied by a sequence of molts, when the existing larval cuticle detaches from the underlying epidermis (apolysis), is partially digested, and eventually shed (ecdysis). Following ecdysis, a new cuticle is synthesized and secreted by the underlying epidermis. When a larva attains full size, it emerges from the food and enters a wandering stage. Within a few hours the larva ceases movement, becomes immobile, and secretes a gluelike substance produced by the salivary glands. The glue proteins allow the larva to adhere to a dry substrate. At this time the insect initiates puparium formation. The third-instar larval (L3) cuticle becomes detached, and a pupal cuticle is secreted. In this molt, however, the L3 cuticle is not discarded but rather is retained and tanned to serve as the external pupal case, which acts to protect the pupa and later the developing adult from infection and desiccation. The pupal stage is followed by adult development, a process known as metamorphosis. The development of the adult fly involves both the histolysis of many larval tissues and organs, the growth and differentiation of adult structures derived from nests of abdominal histoblast cells, and from the growth, expansion, and differentiation of organ anlagen, the imaginal discs. Paired imaginal discs give rise to the adult wings, legs, head, and thoracic structures, and a terminal unpaired disc develops into the external genitalia. The adult that emerges from the pupal case is elegantly adapted both for dispersal (flight) and for reproduction. A detailed review of Drosophila development, from egg to adult, and its hormonal basis can be found in Riddiford (1993), so what follows is a brief summary. The episodic progress of Drosophila development is governed largely by the action and interaction of three hormones-prothoracicotropic hormone (PTTH), a peptide; a cholesterol derived steroid, 20E also referred to in the literature as beta-ecdysone or ecdysterone; and a sesquiterpene, JH. The basic formula for development in larvae is that PTTH triggers the synthesis and release of ecdysone from the prothoracic gland, which is then converted to its active form, 20E, by a 20-monooxidase located in the mitochondria of larval fat body and in other target tissues (Mitchell and Smith, 1988). 20-Hydroxyecdysone subsequently initiates the molt cycle. The type of molt that takes place depends on the titer of JH, which fluctuates during the life cycle (Bownes and Rembold, 1987; Sliter et al., 1987). In the presence of high JH titers, a larval cuticle is replaced by another larval cuticle. At the end of the L3 stage, the JH titer is low and after several minor peaks of 20E secretion, a major peak of 20E initiates puparium formation and the synthesis of the pupal cuticle. After head eversion, the pupal stage is complete. As with Manduca, low JH titers during the larva-pupa transition likely prevent the precocious adult differentiation of imaginal discs (Kiguchi and Riddiford, 1978). The onset of adult development requires a major peak of 20E secretion in the total absence of JH. As discussed in the later section, 20E and JH also have important functions in the adult, promoting both reproductive maturation (Bownes, 1989) and the stereotyped patterns of mating behavior (Manning, 1966). Later sections discuss features of the three hormones that are relevant for understanding of JH function. © 2005 Elsevier Inc. All rights reserved.