Prothoracicotropic hormone modulates environmental adaptive plasticity through the control of developmental timing

Abstract

Adult size and fitness are controlled by a combination of genetics and environmental cues. In , growth is confined to the larval phase and final body size is impacted by the duration of this phase, which is under neuroendocrine control. The neuropeptide prothoracicotropic hormone (PTTH) has been proposed to play a central role in controlling the length of the larval phase through regulation of ecdysone production, a steroid hormone that initiates larval molting and metamorphosis. Here, we test this by examining the consequences of null mutations in the gene for development. Loss of causes several developmental defects, including a delay in developmental timing, increase in critical weight, loss of coordination between body and imaginal disc growth, and reduced adult survival in suboptimal environmental conditions such as nutritional deprivation or high population density. These defects are caused by a decrease in ecdysone production associated with altered transcription of ecdysone biosynthetic genes. Therefore, the PTTH signal contributes to coordination between environmental cues and the developmental program to ensure individual fitness and survival.

Motoneuron-derived Activinβ regulates Drosophila body size and tissue-scaling during larval growth and adult development

“…The most well characterized factors that regulate insect body size are all systemic signals such as juvenile hormone, ecdysone and the IIS/TOR pathways (REWITZ et al 2013;MIRTH AND SHINGLETON 2014;BOULAN et al 2015; KOYAMA AND MIRTH 2018). For example, Ptth mutants delay ecdysone accumulation allowing larvae to grow for an additional 24 hours ultimately leading to larger flies (SHIMELL et al 2018). In this report, we demonstrate that Act, although it is expressed in the PTTH-producing neurons, does not appear to affect ecdysone signaling since Act loss affects neither critical weight nor developmental timing.…”

“…During the final larval stage, a pulse of 20E extinguishes feeding, terminates growth and initiates pupariation. The timing of the 20E pupariation pulse is triggered, in part, by the neuropeptide prothoracicotropic hormone (PTTH) which in Drosophila is produced by the two pairs of neurons in each brain hemisphere that innervate the prothoracic gland (PG) (MCBRAYER et al 2007;SHIMELL et al 2018). PTTH binds to its receptor Torso and stimulates synthesis and secretion of ecdysone from the PG (REWITZ et al 2009;YAMANAKA et al 2013a).…”

“…PTTH binds to its receptor Torso and stimulates synthesis and secretion of ecdysone from the PG (REWITZ et al 2009;YAMANAKA et al 2013a). PTTH production/release responds to a variety of environmental signals including nutritional status, light, and tissue damage as well as internal signals such as juvenile hormone (JH) to further tune the timing of pupariation (YAMANAKA et al 2013b;DE LOOF et al 2015;SHIMELL et al 2018).…”

The histone demethylase KDM5 controls developmental timing inDrosophilaby promoting prothoracic gland endocycles

“…In addition, we tested tissues linked to the regulation of larval growth such as the hormone-producing larval prothoracic gland, insulin secreting cells of the brain, or cells of the fat body that coordinate larval growth with feeding and nutritional status (Yamanaka et al, 2013). Significantly, all Gal4 drivers that were expressed in the larval prothoracic gland significantly rescued kdm5 140 lethality, including spookier-Gal4 (spok-Gal4), which is expressed exclusively in this tissue (Table 1) (Hrdlicka et al, 2002, Moeller et al, 2017, Shimell et al, 2018. Consistent with KDM5 playing critical functions in the ecdysone-secreting larval prothoracic gland, spok-Gal4-mediated re-expression of kdm5 was sufficient to rescue the developmental delay of kdm5 140 ( Figure 1C).…”

“…Drosophila melanogaster offers a genetically amenable model to provide fundamental insight into KDM5 function in vivo, as it encodes a single, highly conserved, kdm5 gene (Gildea et al, 2000). Moreover, in contrast to viable knockouts of KDM5A, KDM5B or KDM5C in mice, loss of Drosophila KDM5 results in lethality , Albert et al, 2013, Iwase et al, 2016, Martin et al, 2018. This allows us to dissect critical functions of KDM5 without the complication of functional redundancy between mammalian KDM5 paralogs that could partially occlude phenotypes.…”