The Upd3 cytokine couples inflammation to maturation defects in Drosophila

Romão, Daniela; Muzzopappa, Mariana; Barrio, Lara; Milán, Marco

doi:10.1016/j.cub.2021.01.080

Cited by 24 publications

(17 citation statements)

References 38 publications

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“…While we were finishing our study, the group of Marco Milan reported that Upd3 signals from the tumor to the PG to delay metamorphosis (Romão et al, 2021), consistent with our findings.…”

Section: Discussionsupporting

confidence: 88%

“…All these results suggest that Apt may be a target mediating the effect of JAK/STAT signaling both normal development and in response to tissue damage. A recent study, published while this manuscript was in preparation, found microRNA bantam (ban) was upregulated downstream of JAK/STAT signaling in the PG (Romão et al, 2021). We checked the effect of ban overexpression in the PG and found that it could also induce PG overgrowth (Fig.…”

Section: Jak/stat Activation Upregulates Apontic In the Pgmentioning

confidence: 97%

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Intrinsic and tumor-induced JAK/STAT signaling regulate developmental timing by the Drosophila prothoracic gland

Cao

Pastor-Pareja

2021

Preprint

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Development involves tightly paced, reproducible sequences of events, yet it must adjust to conditions external to it, such as resource availability and organismal damage. A major mediator of damage-induced immune responses in vertebrates and insects is JAK/STAT signaling. At the same time, JAK/STAT activation by the Drosophila Upd cytokines is pleiotropically involved in normal development of multiple organs. Whether inflammatory and developmental roles of JAK/STAT intersect is unknown. Here, we show that JAK/STAT is active during development of the prothoracic gland (PG), the organ that controls metamorphosis onset through ecdysone production. Reducing JAK/STAT signaling decreased PG size and slightly advanced metamorphosis. Conversely, JAK/STAT hyperactivation, achieved through overexpression of pathway components or SUMOylation loss, caused PG hypertrophy and metamorphosis delay. Interestingly, tissue damage and tumors, known to secrete Upd cytokines, also activated JAK/STAT in the PG and delayed metamorphosis. Finally, we show that expression of transcription factor Apontic, a JAK/STAT target in the PG, recapitulates PG hypertrophy and metamorphosis delay. JAK/STAT damage signaling, therefore, regulates metamorphosis onset at least in part by coopting its developmental role in the PG.Summary statementDamage signaling from tumors mediated by JAK/STAT-activating Upd cytokines delays the Drosophila larva-pupa transition through cooption of a JAK/STAT developmental role in the prothoracic gland.

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“…While we were finishing our study, the group of Marco Milan reported that Upd3 signals from the tumor to the PG to delay metamorphosis (Romão et al, 2021), consistent with our findings.…”

Section: Discussionsupporting

confidence: 88%

Section: Jak/stat Activation Upregulates Apontic In the Pgmentioning

confidence: 97%

Intrinsic and tumor-induced JAK/STAT signaling regulate developmental timing by the Drosophila prothoracic gland

Cao

Pastor-Pareja

2021

Preprint

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“…Interestingly, note that Upd2 is secreted from the fat body into hemolymph ( Rajan and Perrimon, 2012 ) and therefore may provide a nutrient storage signal to the PG that could be an important regulator of developmental timing, perhaps under certain types of non-standard laboratory growth conditions. It has also been recently demonstrated that inflammation-triggered release of Upd3 acts on the PG to produce developmental delay, indicating that the Jak/Stat pathway may be an important sensor for imbalance of various types of physiological processes ( Romão et al, 2021 ).…”

Section: Discussionmentioning

confidence: 99%

Coordination among multiple receptor tyrosine kinase signals controls Drosophila developmental timing and body size

Pan

O’Connor

2021

Cell Reports

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“…Malnutrition or disease can impair growth and delay puberty, whereas obese children enter puberty early [2]. Similarly, Drosophila larvae exposed to poor nutrition, tissue damage, or inflammation delay their development, while rich conditions promote rapid growth and maturation [1,[45][46][47]. These environmental factors are coupled to the appropriate production of steroids via internal checkpoints, one of which is a nutritional-dependent critical weight required to initiate the maturation process [8].…”

Section: Discussionmentioning

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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The Upd3 cytokine couples inflammation to maturation defects in Drosophila

Cited by 24 publications

References 38 publications

Intrinsic and tumor-induced JAK/STAT signaling regulate developmental timing by the Drosophila prothoracic gland

Intrinsic and tumor-induced JAK/STAT signaling regulate developmental timing by the Drosophila prothoracic gland

Coordination among multiple receptor tyrosine kinase signals controls Drosophila developmental timing and body size

Insulin signaling couples growth and early maturation to cholesterol intake

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