Appropriate cell-cell signaling is crucial for proper tissue homeostasis. Protein sorting of cell surface receptors at the early endosome is important for both the delivery of the signal and the inactivation of the receptor, and its alteration can cause malignancies including cancer. In a genetic screen for suppressors of the pro-apoptotic gene hid in Drosophila,we identified two alleles of vps25, a component of the ESCRT machinery required for protein sorting at the early endosome. Paradoxically,although vps25 mosaics were identified as suppressors of hid-induced apoptosis, vps25 mutant cells die. However, we provide evidence that a non-autonomous increase of Diap1 protein levels, an inhibitor of apoptosis, accounts for the suppression of hid. Furthermore, before they die, vps25 mutant clones trigger non-autonomous proliferation through a failure to downregulate Notch signaling, which activates the mitogenic JAK/STAT pathway. Hid and JNK contribute to apoptosis of vps25 mutant cells. Inhibition of cell death in vps25 clones causes dramatic overgrowth phenotypes. In addition, Hippo signaling is increased in vps25 clones, and hippo mutants block apoptosis in vps25 clones. In summary,the phenotypic analysis of vps25 mutants highlights the importance of receptor downregulation by endosomal protein sorting for appropriate tissue homeostasis, and may serve as a model for human cancer.
The Company of Biologists Workshops
For the last 15 years, our publisher, The Company of Biologists, has provided an apt environment to inspire biology and support biologists through our Workshops series. Read about the evolution of the Workshop series and revisit JEB's experience with hosting the first Global South Workshop.
Call for papers – Lifelong Development: the Maintenance, Regeneration and Plasticity of Tissues
Development invites you to submit your latest research to our upcoming special issue – Lifelong Development: the Maintenance, Regeneration and Plasticity of Tissues. This issue will be coordinated by Guest Editors Meritxell Huch (Max Planck Institute of Molecular Cell Biology and Genetics, Germany) and Mansi Srivastava (Harvard University and Museum of Comparative Zoology, USA), working alongside our team of academic Editors. Submit your articles by 30 May 2025.
Meet our 2025 Pathway to Independence (PI) fellows
We are delighted to announce our third cohort of PI fellows - researchers whom we will be supporting as they transition from postdoc to Principal Investigator. Read about the eight talented fellows chosen, whom we're excited to be working with as they navigate the job market.
A case for broadening our view of mechanism in developmental biology
In this Perspective, B. Duygu Özpolat and colleagues survey researchers on their views on what it takes to infer mechanism in developmental biology. They examine what factors shape our idea of what we mean by ‘mechanism’ and suggest a path forward that embraces a broad outlook on the diversity of studies that advance knowledge in our field.
the Node: Have your say
Our community site, the Node, is conducting a user survey about the content and the design of the site. Help us shape the Node's future and thank you for being a part of the Node over the last 15 years.
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