bioRxiv Science⌕ Search

Biology subjects

Boulan, L.

Publications and source records attributed to Boulan, L..

4 recordsLinked to original sources

Xrp1 integrates cellular stress through different control modes in Drosophila

Cells and tissues have the ability to respond to different stresses and maintain their homeostasis. The b-Zip transcription factor Xrp1 was found to play a pivotal role in this context in Drosophila. Xrp1 is required for the response to irradiation, in genetic conditions of ribosomal protein (Rp) deficiency leading to cell competition, and more generally in mediating the Integrated Stress Response (ISR). However, how these diverse stresses converge to and activate Xrp1 is still unclear. Our results demonstrate the existence of three separate mechanisms of Xrp1 induction. In response to Rp stress, a short isoform of Xrp1 is produced and requires the function of the ribosomal protein RpS12. In response to irradiation, a specific mRNA isoform is transcriptionally induced, which encodes the Xrp1-short protein isoform, in a p53-dependent manner. In response to the ISR, the long isoform of Xrp1 is translated by the derepression of a uORF present on the Xrp1 5'UTR, a mechanism that requires eIF2 phosphorylation, RpS12, and a transcriptional induction by ATF4. Therefore, our work provides a comprehensive understanding of the role of Xrp1 in different situations of cellular stress, illustrating the complex level of integration of the mechanisms controlling this central gene.

developmental biology↗

A switch in the mode of tissue growth extends the growth phase of Drosophila wing primordia during early pupal development

Understanding how final organ size is established during development raises two key questions: how organs increase their mass and how they stop growing upon reaching an appropriate size. While organ growth is driven by conserved signaling pathways, the mechanisms underlying growth arrest remain elusive. Studies on Drosophila imaginal wing discs have provided a model whereby final organ size coincides with an arrest of cell proliferation at the end of the larval phase. Here, through 3D reconstruction and volume measurements, we show that wing discs grow continuously throughout the larva-to-pupa (L/P) transition and proceed to growth arrest later during the pupal period. This supplemental growth phase involves a switch at the L/P transition that uncouples proliferation from tissue growth, with an important contribution from Insulin/IGF signaling. These findings challenge the existing model of imaginal wing development and open new avenues for our understanding of growth arrest and organ size determination.

developmental biology↗

Dilp8 controls a time window for tissue size adjustment in Drosophila

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.

developmental biology↗

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

How organs scale with other body parts is not mechanistically understood. We have addressed this question using the Drosophila imaginal disc model. When growth of one disc domain is perturbed, other parts of the disc and other discs slow down their growth, maintaining proper inter-disc and intra-disc proportions. We show here that the relaxin-like Dilp8 is required for this inter-organ coordination. Our work also reveals that the stress-response transcription factor Xrp1 plays a key role upstream of dilp8 in linking organ growth status with non-autonomous/systemic growth response. In addition, we show that the small ribosomal subunit protein RpS12 is required to trigger Xrp1-dependent non-autonomous response. Our work demonstrates that RpS12, Xrp1 and Dilp8 constitute a new, independent regulatory module that ensures intra- and inter-organ growth coordination during development.

developmental biology↗