Search bioRxiv⌕ Search
Home/Archive/bioRxiv

bioRxiv · 10.64898/2025.12.16.694615

Gadd45 regulates fate decisions of myeloid-type blood progenitor cells in Drosophila

Jaiswal, P.·Mondal, B. C.
View original source ↗Export metadata ↓

Abstract

Gadd45 is a highly conserved stress response protein that interacts with multiple cellular proteins, playing a crucial role in regulating the cell cycle and responding to various forms of stress. Altered expression of Gadd45 is linked to several solid tumors and hematopoietic malignancies. It is also identified as a gene crucial for cytokine-induced myeloid differentiation, although the precise molecular mechanisms underlying this process remain unclear. We utilized the Drosophila hematopoietic system to investigate the role of Gadd45 in the development of myeloid-type blood cells, employing in vivo genetics and cell biological methods. We show that the absence of Gadd45 reduces the number of crystal cells but does not significantly impact macrophage-like cell plasmatocyte differentiation. However, Gadd45 overexpression caused intermediate progenitors to differentiate into lamellocytes and plasmatocytes to transdifferentiate into lamellocytes, a response typically observed during larval stages in response to immune challenges and injury. Interestingly, Gadd45 overexpression initiated the lamellocyte differentiation program by activating a combination of Toll, JNK, and JAK/STAT signaling pathways. This closely resembles the process by which specialized macrophages are derived in mammals. Moreover, Gadd45 overexpression does not induce cell death but alters the cell cycle status of hematopoietic progenitor cells. This study enhances our understanding of how Gadd45 functions during myeloid cell development. Significance StatementO_LILoss of Gadd45 causes a reduction in crystal cells but does not significantly impact macrophage-like plasmatocyte differentiation. C_LIO_LIGadd45 overexpression causes myeloid-type progenitor cells to differentiate into lamellocyte, as well as plasmatocyte transdifferentiate to lamellocyte. Gadd45 triggers differentiation by activating a combination of Toll, JNK, and JAK/STAT signaling pathways. C_LIO_LIOverexpressing Gadd45 does not induce apoptosis but alters the cell cycle behavior of hematopoietic progenitor cells. C_LI

Explore related subjects

developmental biologyPreprint

Keep this discovery

Explore connections, maps & timelines

BibTeXRIS

Jaiswal, P., Mondal, B. C.. 2025-12-18. Gadd45 regulates fate decisions of myeloid-type blood progenitor cells in Drosophila. https://doi.org/10.64898/2025.12.16.694615

Cite the original work for its findings. Save a collection to share your selection of sources.

KEEP EXPLORING

Related preprints

bioRxiv2026

Cell Position-Associated Division Orders and Cell Cycle Durations Shape Asymmetric Trajectories of Cell Fates and Morphological Events in Pre- and Peri-implantation Mouse Embryos

A central question in developmental biology is how spatiotemporal embryo morphological events and cell differentiation are precisely coordinated to eventually develop into a mature organism. Previous research has shown cell positions and asymmetric division stages are related to cell lineage specification since morula stage. However, the detailed spatiotemporal dynamics and histories of embryonic cells and their relations with cell lineage specification remain incompletely understood from the onset of embryo development onward. My study on in-vitro embryos showed that continuous live cell tracking mapped community-like patterns in cell origin and differentiation. Cell positions, cell temporal factors (such as cell division order and cell cycle) and their histories intricately interacted over pre- and peri-implantation stages. These interactions of spatiotemporal cellular activities directed embryo morphological events and asymmetric cell lineage origin and differentiation throughout 2-cell to around 100-cell stage. In conclusion, this study provides comprehensive insights into the cellular spatiotemporal dynamics of cell inheritance and differentiation during pre- and peri-implantation morphological events and cell lineage specification. By longitudinally integrating spatial and temporal parameters relating to early embryogenesis, the findings not only bridge divergent explanations stemmed from different studies in the field but also offers a refined foundation for evaluating embryo potential and improving outcomes in assisted reproductive technologies, stem cell research, and regenerative medicine.

developmental biology↗
bioRxiv2026

Proteome-wide quantification of protein turnover in frog and fly embryos reveals divergent strategies of maternal inheritance

Every embryo inherits a maternal proteome that it must remodel with zygotic proteins to build its many cell types. The fate of the maternal proteome remains contested because indirect measurements cannot resolve it. Here, we combine 18O-water labeling with multiplexed proteomics to quantify protein turnover proteome-wide in frog and fly embryos. Through hatching, the frog preserves the bulk of its maternal proteome, confining rapid degradation to a small regulatory module. The fly cannot meet its synthesis demand from yolk alone and instead degrades nearly all maternal proteins, including housekeeping proteins long assumed stable, recycling them into new protein. Yet the turnover hierarchy is conserved, with disordered and regulatory proteins degrading fastest, while the fly rescales the whole proteome ~eightfold faster. These results recast the developmental proteome as both informational inheritance and metabolic reserve, establish 18O-water labeling as a turnover method for non-feeding organisms, and provide a resource of embryonic half-lives.

developmental biology↗
bioRxiv2026

The MAPK phosphatase VHP-1 buffers pharynx-to-body proportions against tissue-specific growth imbalance in C. elegans

Maintaining appropriate organ size ratios in the face of growth fluctuations is critical for the development of a reproducible body plan. Yet the mechanisms involved remain poorly understood. Here, we investigated how pharynx-to-body proportions are maintained in Caenorhabditis elegans, combining tissue-specific perturbations, genetic screening, and longitudinal live imaging. A genome-wide RNAi screen revealed that knock-down of the dual-specificity MAPK phosphatase VHP-1 turns animals hypersensitive to inter-tissue growth imbalance caused by pharyngeal or epidermal depletion of the mTORC1 activator RAGA-1 or the ribosomal protein RPL-22. In contrast, vhp-1 mutants tolerated global raga-1 loss, indicating a specific requirement for vhp-1 under tissue growth imbalance. Knock-down of the p38 pathway suppressed the imbalance-specific defects of vhp-1 mutants. In contrast, JNK knock-down effectively rescued the pleiotropic phenotypes of vhp-1 mutants but only weakly reduced their sensitivity to RAGA-1 imbalance, indicating that these two stress-MAPK pathways make distinct contributions to the response to growth imbalance. Finally, whole-animal VHP-1 levels increased upon epidermal RAGA-1 depletion, and epidermal VHP-1 depletion did not reproduce the sensitivity caused by global vhp-1 loss, consistent with a contribution from VHP-1 outside the growth-perturbed epidermis in buffering against local growth imbalance.

developmental biology↗