Ecdysone-dependent cell death during metamorphosis in the hemimetabolous insect Blattella germanica

Abstract

Metamorphosis in holometabolous insects is entailed on the destruction of larval tissues. Intensive research in Drosophila melanogaster, a model of holometabolan metamorphosis, has shown that the steroid hormone 20-hydroxyecdysone (20E) signals programmed cell death (PCD) of larval tissues during metamorphosis. However, D. melanogaster shows a highly derived type of development and the mechanisms regulating PCD may not be representative in the insect class context. Unlike the holometabolous, hemimetabolous species hatch from the egg as first instar nymphs that resemble miniature adults. In these insects, growth and maturation occur simultaneously throughout sequential nymphal stages until the imaginal molt. Nevertheless, the absence of an intermediate pupal stage in hemimetabolous insects does not imply the lack of stage-specific PCD. In this sense, using the German cockroach Blattel la germanica as a hemimetabolan model, we have showed that the prothoracic gland, which is responsible for the synthesis of ecdysteroids, undergoes a precise developmentally controlled degeneration after the imaginal molt. In this work, we show a detailed characterization of the molecular mechanisms that coordinate the degeneration of the PG of B. germanica. First, we show that this insect has an Inhibitor of Apoptosis Protein (BgIAP-1) that is constantly required to block premature PCD during nymphal devel opment. Moreover, we demonstrate that a complex 20E-triggered hierarchy of transcription factors (BgEcR, BgRXR, BgE75, BgHR3 and BgHR4), converging to a strong activation of the death inducer Fushi tarazu-factor 1 (BgFTZ-F1) during the nymphal-adult transition, controls the prothoracic gland degeneration. We also show that this degeneration is prevented by juvenile hormone, and that this anti-apoptotic effect is mediated, in part, through down-regulation of BgFTZ-F1 expression. Given the relevance of PCD in the metamorphic process, the characterization of the molecular mechanisms regulating PCD in hemimetabolous insects would allow help to elucidate how metamorphosis has evolved from less to more derived insect species.