On the evolutionary developmental biology of the cell

Trends in Genetics, Journal Year: 2024, Volume and Issue: 40(10), P. 822 - 833

Published: July 5, 2024

Organisms are complex assemblages of cells, cells that produce light, shoot harpoons, and secrete glue. Therefore, identifying the mechanisms generate novelty at level individual cell is essential for understanding how multicellular life evolves. For decades, field evolutionary developmental biology (Evo-Devo) has been developing a framework connecting genetic variation arises during embryonic development to emergence diverse adult forms. With increasing access new single 'omics technologies an array techniques manipulating gene expression, we can now extend these inquiries inward cell. In this opinion, I argue applying Evo-Devo makes it possible explore natural history where was once only organismal level.

Language: Английский

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Single-cell genomic profiling to study regeneration

Current Opinion in Genetics & Development, Journal Year: 2024, Volume and Issue: 87, P. 102231 - 102231

Published: July 24, 2024

Regenerative capacities and strategies vary dramatically across animals, as well between cell types, organs, with age. In recent years, high-throughput single-cell transcriptomics other profiling technologies have been applied to many animal models gain an understanding of the cellular molecular mechanisms underlying regeneration. Here, we review studies regeneration in diverse contexts summarize key concepts that emerged. The immense regenerative capacity some invertebrates, exemplified by planarians, is driven mainly differentiation abundant adult pluripotent stem cells, whereas cases, involves reactivation embryonic or developmental gene-regulatory networks differentiated types. However, also differs from development ways, including use regeneration-specific types gene regulatory networks.

Language: Английский

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PDK-1/S6K and mTORC1 bypass systemic growth restrictions to promote regeneration

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2024, Volume and Issue: unknown

Published: Aug. 6, 2024

Abstract Tissue damage and inflammation trigger systemic signals that induce catabolic breakdown nutrient release in distant organs, a process well-characterized the context of tumor cachexia. While mechanisms allowing tumors to circumvent these growth restrictions are known, physiological processes overcome inflammation-induced support tissue repair regeneration remain largely unexplored. In our study, we use model developing Drosophila imaginal discs dissect key metabolic signaling adaptations help restrictions. Our findings reveal unique strategy used by rapidly proliferating cells regenerating domain. Instead relying on conventional Insulin-PI3K-Akt pathway, utilize JAK/STAT-PDK1-S6K axis. This adaptation facilitates sustained protein synthesis cellular despite catabolism associated with low insulin signaling. Specifically, find fat body is driven insulin-binding factor Impl2, which expressed at site inflammatory damage. Notably, regenerative proliferation also supported mTORC1 activity upregulation amino acid transporters These align specific metabolite signature hemolymph, revealing specialized program meets demands fast-proliferating cells. work provides insight into how tissues rewire pathways adapt their coordinate conserved provision response. have important implications for understanding human diseases such as chronic wounds cancer.

Language: Английский

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Xrp1 governs the stress response program to spliceosome dysfunction

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2023, Volume and Issue: unknown

Published: April 6, 2023

ABSTRACT Co-transcriptional processing of nascent pre-mRNAs by the spliceosome is vital to regulating gene expression and maintaining genome integrity. Here, we show that deficiency functional U5 snRNPs in Drosophila imaginal cells causes extensive transcriptome remodeling accumulation highly mutagenic R-loops, triggering a robust stress response cell cycle arrest. Despite compromised proliferative capacity, snRNP deficient increased protein translation size, causing intra-organ growth disbalance before being gradually eliminated via apoptosis. We identify Xrp1-Irbp18 heterodimer as primary driver transcriptional cellular program downstream malfunction. Knockdown Xrp1 or Irbp18 attenuated JNK p53 activity, restored normal progression growth, inhibited death. Reducing Xrp1-Irbp18, however, did not rescue splicing defects organismal lethality, highlighting requirement accurate for tissue homeostasis. Our work provides novel insights into crosstalk between DNA damage defines critical sensor

Language: Английский

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