Ecdysone signaling at metamorphosis triggers apoptosis of Drosophila abdominal muscles

Abstract

One of the most dramatic examples of programmed cell death occurs during Drosophila metamorphosis, when most of the larval tissues are destroyed in a process termed histolysis. Much of our understanding of this process comes from analyses of salivary gland and midgut cell death. In contrast, relatively little is known about the degradation of the larval musculature. Here, we analyze the programmed destruction of the abdominal dorsal exterior oblique muscle (DEOM) which occurs during the first 24 hrs of metamorphosis. We find that ecdysone signaling through Ecdysone receptor isoform B1 is required cell autonomously for the muscle death. Furthermore, we show that the orphan nuclear receptor FTZ-F1, opposed by another nuclear receptor, HR39, plays a critical role in the timing of DEOM histolysis. Finally, we show that unlike the histolysis of salivary gland and midgut, abdominal muscle death occurs by apoptosis, and does not require autophagy. Thus, there is no set rule as to the role of autophagy and apoptosis during Drosophila histolysis.

Steroid signaling promotes stem cell maintenance in the Drosophila testis

“…Ecdysone signaling is known to regulate apoptosis during development, and in the ovary, developing germline cysts lacking ecdysone signaling die more often than control cysts (Ables and Drummond-Barbosa, 2010; Zirin et al, 2013). Therefore, we asked whether stem cell loss in EcR ts testes at restrictive temperature could be caused by increased cell death.…”

Ecdysone-mediated programmed cell death in Drosophila

“…This subset aids in the formation of the adult musculature but dies shortly after fly eclosure (Bate et al, 1991, Broadie and. Ecdysone-mediated apoptosis is required for DEOM PCD as knockdown of EcR-B1 that is highly expressed in this tissue delays degradation and caspase activation (Zirin et al, 2013). Autophagy is observed but is not essential for caspase activation or DEOM degradation as this occurs normally despite knockdown of key components of the autophagy pathway.…”

“…During the middle of the third instar larval stage, low-titre pulses of ecdysone trigger a switch in the mechanism of caspase activation from apoptosome-independent to apoptosome-dependent through upregulation of the apoptosome components dark and dronc as well as drice (Kang and Bashirullah, 2014). Towards the end of the third instar larval stage a high-titre pulse of ecdysone initiates larval-pupal metamorphosis and destruction of the larval midgut, and abdominal and anterior muscles (Cakouros et al, 2004b, Fahrbach et al, 2005, Jiang et al, 1997, Lee et al, 2002a, Yin and Thummel, 2005, Zirin et al, 2013. A second pulse of ecdysone approximately 12 hours after puparium formation (h APF) signals the transition from prepupal to pupal development and initiates PCD of the larval salivary glands (Jiang et al, 1997, Lee et al, 2002b.…”

“…DEOMs begin degrading at 8h APF with the majority of DEOMs degraded by 12h APF (Zirin et al, 2013). The timing of DEOM cell death is regulated by the nuclear receptors bFTZ-F1 and HR39 which have opposite expression profiles in both muscle types.…”

“…In Drosophila, developmentally timed pulses of the steroid hormone 20-hydroxyecdysone (ecdysone) initiates processes such as molting and larval-pupal metamorphosis (Riddiford et al, 2000, Thummel, 2001. Of these processes, ecdysone induces the histolysis of many obsolete larval tissues during larval-pupal metamorphosis such as the midgut, salivary gland, anterior and abdominal muscles, and distinct subsets of neurons in the nervous system and optic lobe (Choi et al, 2006, Fahrbach et al, 2005, Hara et al, 2013, Jiang et al, 1997, Kumar and Cakouros, 2004, Lee et al, 2002a, Winbush and Weeks, 2011, Zirin et al, 2013. Additionally, ecdysone is important for the remodelling of the fat body and nervous system (Boulanger and Dura, 2014, Kirilly et al, 2009, Kuo et al, 2005, T. , Loncle and Williams, 2012, Rusten et al, 2004, Williams and Truman, 2005.…”