Snail synchronizes endocycling in a TOR-dependent manner to coordinate entry and escape from endoreplication pausing during the Drosophila critical weight checkpoint

Zeng, Jie; Huynh, Nhan; Phelps, Brian; King-Jones, Kirst

doi:10.1371/journal.pbio.3000609

Cited by 26 publications

(28 citation statements)

References 97 publications

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“…TOR signaling promotes endoreduplicative genome amplification in the PG during L3 via the transcription factor Snail, which is important for the CW checkpoint, described below (Ohhara et al 2017;Zeng et al 2020). Several transcription factors have also been shown to regulate the expression of the ecdysone-biosynthetic genes specifically.…”

Section: Control Of Prothoracicotropic Hormone Releasementioning

confidence: 99%

Regulation of Body Size and Growth Control

Texada¹,

Kaburagi²,

Rewitz³

2020

Genetics

116

146

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The control of body and organ growth is essential for the development of adults with proper size and proportions, which is important for survival and reproduction. In animals, adult body size is determined by the rate and duration of juvenile growth, which are influenced by the environment. In nutrient-scarce environments in which more time is needed for growth, the juvenile growth period can be extended by delaying maturation, whereas juvenile development is rapidly completed in nutrient-rich conditions. This flexibility requires the integration of environmental cues with developmental signals that govern internal checkpoints to ensure that maturation does not begin until sufficient tissue growth has occurred to reach a proper adult size. The Target of Rapamycin (TOR) pathway is the primary cell-autonomous nutrient sensor, while circulating hormones such as steroids and insulin-like growth factors are the main systemic regulators of growth and maturation in animals. We discuss recent findings in Drosophila melanogaster showing that cell-autonomous environment and growth-sensing mechanisms, involving TOR and other growth-regulatory pathways, that converge on insulin and steroid relay centers are responsible for adjusting systemic growth, and development, in response to external and internal conditions. In addition to this, proper organ growth is also monitored and coordinated with whole-body growth and the timing of maturation through modulation of steroid signaling. This coordination involves interorgan communication mediated by Drosophila insulin-like peptide 8 in response to tissue growth status. Together, these multiple nutritional and developmental cues feed into neuroendocrine hubs controlling insulin and steroid signaling, serving as checkpoints at which developmental progression toward maturation can be delayed. This review focuses on these mechanisms by which external and internal conditions can modulate developmental growth and ensure proper adult body size, and highlights the conserved architecture of this system, which has made Drosophila a prime model for understanding the coordination of growth and maturation in animals.

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Section: Control Of Prothoracicotropic Hormone Releasementioning

confidence: 99%

Regulation of Body Size and Growth Control

Texada¹,

Kaburagi²,

Rewitz³

2020

Genetics

116

146

View full text Add to dashboard Cite

show abstract

“…Furthermore, activating insulin/TOR signaling in the PG induces precocious critical-weight attainment, whereas reducing it delays this [ 9 , 22 , 45 , 46 , 106 , 114 ]. One hypothesis proposes that this small nutrient-sensitive ecdysone peak is caused by increased insulin signaling [ 106 ]; another holds that nutrient-dependent TOR-mediated progression of endocycles of chromosomal replication in the cells of the PG leads to an irreversible activation of ecdysone biosynthesis that triggers the critical-weight transition [ 110 , 115 ]. Notably, these hypotheses are not mutually exclusive, and perhaps rising insulin signaling is able to activate an ecdysone pulse only after enough chromosomal duplication has occurred to induce a transcriptional state that commits the PG to synthesize ecdysone.…”

Section: Adaptation Of Larval Growth and Developmentmentioning

confidence: 99%

Metabolism and growth adaptation to environmental conditions in Drosophila

Kaburagi

Texada

Halberg

et al. 2020

Cell. Mol. Life Sci.

104

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Organisms adapt to changing environments by adjusting their development, metabolism, and behavior to improve their chances of survival and reproduction. To achieve such flexibility, organisms must be able to sense and respond to changes in external environmental conditions and their internal state. Metabolic adaptation in response to altered nutrient availability is key to maintaining energy homeostasis and sustaining developmental growth. Furthermore, environmental variables exert major influences on growth and final adult body size in animals. This developmental plasticity depends on adaptive responses to internal state and external cues that are essential for developmental processes. Genetic studies have shown that the fruit fly Drosophila, similarly to mammals, regulates its metabolism, growth, and behavior in response to the environment through several key hormones including insulin, peptides with glucagon-like function, and steroid hormones. Here we review emerging evidence showing that various environmental cues and internal conditions are sensed in different organs that, via inter-organ communication, relay information to neuroendocrine centers that control insulin and steroid signaling. This review focuses on endocrine regulation of development, metabolism, and behavior in Drosophila, highlighting recent advances in the role of the neuroendocrine system as a signaling hub that integrates environmental inputs and drives adaptive responses.

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“…Nutrition influences ecdysone production through insulin and PTTH as well as TOR signaling in the PG itself [13,30,39,40]. The TOR-mediated mechanism in the PG couples nutritional inputs to endocycling, which in turn is linked to CW [41,42]. We therefore asked whether cholesterol levels in the PG affect these events.…”

Section: Enhanced Cholesterol Signaling In the Pg Alters The Nutritional Checkpoint That Prevents Precocious Initiation Of Maturationmentioning

confidence: 99%

“…Since cholesterol sensing appears to drive endureduplication, and endoreduplication drives the irreversible activation of the pupariation-inducing neuroendocrine axis at CW [41,42], we therefore investigated whether increasing PG cholesterol by knockdown of Npc1a would reduce CW -that is, if it might cause animals to overestimate their overall body size and therefore pupariate inappropriately. We used the druginducible phantom-GeneSwitch-GAL4 (phm GS >) driver to induce Npc1a-RNAi in the PG in mid-L2 by treatment with dietary RU486.…”

Section: Enhanced Cholesterol Signaling In the Pg Alters The Nutritional Checkpoint That Prevents Precocious Initiation Of Maturationmentioning

confidence: 99%

Insulin signaling couples growth and early maturation to cholesterol intake

Texada

Lassen

Pedersen

et al. 2021

Preprint

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Nutrition is one of the most important influences on growth and the timing of developmental maturation transitions including mammalian puberty and insect metamorphosis. Childhood obesity is associated with precocious puberty, but the assessment mechanism that links body fat to early maturation is unknown. During development, intake of nutrients promotes signaling through insulin-like systems that govern the growth of cells and tissues and also regulates the timely production of the steroid hormones that initiate the juvenile-adult transition. We show here that the dietary lipid cholesterol, required as a component of cell membranes and as a substrate for steroid biosynthesis, also governs body growth and maturation in Drosophila via promoting the expression and release of insulin-like peptides. This nutritional input acts via the Niemann-Pick-type-C (Npc) cholesterol sensors/transporters in the glia of the blood-brain barrier and cells of the adipose tissue to remotely drive systemic insulin signaling and body growth. Furthermore, increasing intracellular cholesterol levels in the steroid-producing prothoracic gland strongly promotes endoreduplication, leading to accelerated attainment of a nutritional checkpoint that ensures that animals do not initiate maturation prematurely. These findings couple sensing of the lipid cholesterol to growth control and maturational timing, which may help explain both the link between cholesterol and cancer as well as the critical connection between body fat (obesity) and early puberty.

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Snail synchronizes endocycling in a TOR-dependent manner to coordinate entry and escape from endoreplication pausing during the Drosophila critical weight checkpoint

Cited by 26 publications

References 97 publications

Regulation of Body Size and Growth Control

Regulation of Body Size and Growth Control

Metabolism and growth adaptation to environmental conditions in Drosophila

Insulin signaling couples growth and early maturation to cholesterol intake

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