Inter-organ growth coordination is mediated by the Xrp1/Dilp8 axis in <i>Drosophila</i>

Boulan, Laura; Andersen, Ditte S.; Colombani, Julien; Boone, Émilie; Léopold, Pierre

doi:10.1101/462473

Cited by 11 publications

(17 citation statements)

References 25 publications

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“…DILP8 secretion by slow-growing discs is also necessary for this intra- and interorgan growth coordination, which depends on remote action of DILP8 via neuronal Lgr3 activity and is mediated by the systemic effects of ecdysone ( Colombani et al 2015 ; Vallejo et al 2015 ), which promotes growth of imaginal discs ( Colombani et al 2005 ; Herboso et al 2015 ; Dye et al 2017 ; Moeller et al 2017 ). Feeding with ecdysone prevents DILP8-mediated growth reduction in intact discs ( Boulan et al 2019 ), suggesting that DILP8 secreted from abnormally growing discs suppresses the growth of intact imaginal discs by limiting ecdysone signaling. Although the activation of Lgr3-expressing neurons in the brain mediates the growth coordination of undamaged discs, Lgr3 is also required in the PG itself for growth coordination—not for pupariation delay—during regeneration ( Jaszczak et al 2015 , 2016 ).…”

Section: Body-size Controlmentioning

confidence: 99%

“…Activation of the c-Jun N-terminal kinase (JNK) pathway in the discs is necessary in neoplastic growth conditions for DILP8 induction and pupariation delay, which also depends on cytokine Unpaired-1 (Upd1)-mediated activation of the JAK/STAT pathway in regenerating discs ( Colombani et al 2012 ; Katsuyama et al 2015 ). In slow-growth conditions such as those caused by loss of ribosomal protein genes ( Minute mutants), the stress-responsive transcription factor Xrp1 is required for remote nonautonomous growth inhibition of other discs by DILP8 ( Boulan et al 2019 ). During normal development, Yorkie and Scalloped, the transcriptional effectors of the Hippo pathway (described above), directly regulate DILP8 expression, coupling normal growth and DILP8 expression ( Boone et al 2016 ).…”

Section: Body-size Controlmentioning

confidence: 99%

See 1 more Smart Citation

Regulation of Body Size and Growth Control

Texada¹,

Kaburagi²,

Rewitz³

2020

Genetics

129

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: Body-size Controlmentioning

confidence: 99%

Section: Body-size Controlmentioning

confidence: 99%

Regulation of Body Size and Growth Control

Texada¹,

Kaburagi²,

Rewitz³

2020

Genetics

129

146

View full text Add to dashboard Cite

show abstract

“…Although the mechanism of tissue repair-induced delay by Dilp8 is now better understood 16 , the mechanism by which the Dilp8 hormone controls developmental stability remains unknown. Two distinct hypotheses could account for such control.…”

Section: Introductionmentioning

confidence: 99%

Dilp8 controls a time window for tissue size adjustment inDrosophila

Boulan

Blanco-Obregon

Marzkioui

et al. 2020

Preprint

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The control of organ size mainly relies on precise autonomous growth programs. However, organ development is subject to random variations, called developmental noise, best revealed by the fluctuating asymmetry observed between bilateral organs. The developmental mechanisms ensuring bilateral symmetry in organ size are mostly unknown. In Drosophila, null mutations for the relaxin-like hormone Dilp8 increase wing fluctuating asymmetry, suggesting that Dilp8 plays a role in buffering developmental noise. Here we show that size adjustment of the wing primordia involves a peak of Dilp8 expression that takes place sharply at the end of juvenile growth. Wing size adjustment relies on a crossorgan communication involving the epidermis as the source of Dilp8. We identify ecdysone signaling as both the trigger for epidermal dilp8 expression and its downstream target in the wing primordia, thereby establishing reciprocal feedback between the two hormones as a systemic mechanism controlling organ size precision. Our results reveal a hormone-based time window ensuring fine-tuning of organ size and bilateral symmetry.

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“…Many physiological functions and pathological initiation and progression originate from communication between organs, which occurs via hormones and cytokines, produced by both peripheral organs and the central nervous system (Karsenty and Olson, 2016;Castillo-Armengol et al, 2019). Two excellent examples are inter-organ growth coordination: growth-impaired organs induce the systemic growth inhibition of undamaged organs by producing Dilp8 hormone (Boulan et al, 2019), and endocrine-regulated metabolic homeostasis (Scopelliti et al, 2019). Moreover, the crosstalk between the liver and intestine by FGF19 performs important functions in cholesterol metabolism and energy homeostasis (Castillo-Armengol et al, 2019).…”

Section: Regulation At the Organ Level Inter-organ Signaling Communicmentioning

confidence: 99%

Systemic Regulation of Cancer Development by Neuro-Endocrine-Immune Signaling Network at Multiple Levels

Jiang

Zhang

et al. 2020

Front. Cell Dev. Biol.

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The overarching view of current tumor therapies simplifies cancer to a cell-biology problem in which neoplasms are caused solely by malignant cells and the exploration of carcinogenesis and tumor progression largely focuses on somatic mutations and other genetic abnormalities of cancer cells. The limited therapeutic response indicates that cancer is driven not only by endogenous oncogenic factors and reciprocal interactions within the tumor microenvironment, but also by complex systemic processes. Homeostasis is the fundamental premise of health, and is maintained by systemic regulation of neuro-endocrine-immune axis. Cancer is also a systemic disease that manifested by dysfunction of the nervous, endocrine, and immune systems. Multiple axes of regulation exist in cancer, including central-, organ-, and microenvironment-level manipulation. At each specific regulatory level, the tridirectional communication among the nervous, endocrine, and immune factors transmit flexible signaling to induce proliferation, invasion, reprogrammed metabolism, therapeutic resistance, and other malignant phenotypes of cancer cells, resulting in the extremely poor prognosis of this lethal disease. Understanding this coordinated signaling network will enable the development of new approaches for cancer treatment via behavioral and pharmacological interventions.

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Inter-organ growth coordination is mediated by the Xrp1/Dilp8 axis in Drosophila

Cited by 11 publications

References 25 publications

Regulation of Body Size and Growth Control

Regulation of Body Size and Growth Control

Dilp8 controls a time window for tissue size adjustment inDrosophila

Systemic Regulation of Cancer Development by Neuro-Endocrine-Immune Signaling Network at Multiple Levels

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