Juarez-Carreno, S. | bioRxiv Science

bioRxiv2025

A systemic role of macrophage-derived BMP2/4 homolog Dpp in regulating sterol hormone synthesis under dietary stress

A high-sugar diet (HSD), prevalent in Western countries, compromises the growth and development of children and primes their bodies for chronic diseases. Macrophages, which are immune cells found throughout the body, can sense environmental changes and influence surrounding tissues. Using Drosophila as a model, here we show that macrophages respond to an HSD by increasing the production of Decapentaplegic (Dpp), a protein related to human BMP2/4. Dpp then signals to the endocrine system, the prothoracic gland, to inhibit the synthesis of ecdysone, a crucial steroid hormone that triggers the transition from larva to pupa. By reducing ecdysone synthesis, the larval stage is prolonged. This extended developmental period provides larvae exposed to an HSD more time to reach an optimal size. Our findings highlight how different organs communicate to counteract the negative impact of an HSD during development and expand our understanding of Dpp function, showing that it acts not only as a local developmental signal but also as a systemic regulator.

developmental biology↗

bioRxiv2023

The macrophage genetic cassette inr/dtor/pvf2 is a nutritional status checkpoint for developmental timing.

A small number of signaling molecules, used reiteratively, control differentiation programs, but the mechanisms that adapt developmental timing to environmental cues are less understood. We report here that a macrophage inr/dtor/pvf2 genetic cassette is a developmental timing checkpoint in Drosophila, which either licenses or delays biosynthesis of the steroid hormone in the endocrine gland and metamorphosis according to the larval nutritional status. Insulin-Receptor/dTor signaling in macrophages is required and sufficient for production of the PDGF/VEGF family growth factor Pvf2, which turns on transcription of the sterol biosynthesis Halloween genes in the prothoracic gland via its receptor Pvr. In response to a starvation event or genetic manipulation, low Pvf2 signal delays steroid biosynthesis until it becomes Pvr-independent, thereby prolonging larval growth before pupation. The significance of this developmental timing checkpoint for host fitness is illustrated by the observation that it regulates the size of the pupae and adult flies. One sentence summaryA macrophage Inr/dtor/pvf2 cassette is a nutritional status checkpoint that controls developmental timing via steroid hormone biosynthesis in the endocrine gland.

immunology↗