How clocks and hormones act in concert to control the timing of insect development

During the last century, insect model systems have provided fascinating insights into the endocrinology and developmental biology of all animals. During the insect life cycle, molts and metamorphosis delineate transitions from one developmental stage to the next. In most insects, pulses of the steroid hormone ecdysone drive these developmental transitions by activating signaling cascades in target tissues. In holometabolous insects, ecdysone triggers metamorphosis, the remarkable remodeling of an immature larva into a sexually mature adult. The input from another developmental hormone, juvenile hormone (JH), is required to repress metamorphosis by promoting juvenile fates until the larva has acquired sufficient nutrients to survive metamorphosis. Ecdysone and JH act together as key endocrine timers to precisely control the onset of developmental transitions such as the molts, pupation, or eclosion. In this review, we will focus on the role of the endocrine system and the circadian clock, both individually and together, in temporally regulating insect development. Since this is not a coherent field, we will review recent developments that serve as examples to illuminate this complex topic. First, we will consider studies conducted in Rhodnius that revealed how circadian pathways exert temporal control over the production and release of ecdysone. We will then take a look at molecular and genetic data that revealed the presence of two circadian clocks, located in the brain and the prothoracic gland, that regulate eclosion rhythms in Drosophila. In this context, we will also review recent developments that examined how the ecdysone hierarchy delays the differentiation of the crustacean cardioactive peptide (CCAP) neurons, an event that is critical for the timing of ecdysis and eclosion. Finally, we will discuss some recent findings that transformed our understanding of JH function.