Developmental Biology, Journal Year: 2024, Volume and Issue: unknown
Published: Dec. 1, 2024
Language: Английский
Disease Models & Mechanisms, Journal Year: 2025, Volume and Issue: 18(4)
Published: April 1, 2025
ABSTRACT Drosophila models for tumorigenesis have revealed conserved mechanisms of signaling involved in mammalian cancer. Many these use highly mitotically active tissues. Few adult tissues, when most cells are terminally differentiated and postmitotic. The accessory glands prostate-like a model prostate using this tissue has been explored. In prior model, oncogenic was induced during the proliferative stages gland development, raising question how activity impacts differentiated, postmitotic tissue. Here, we show that leads to activation pro-tumorigenic program, similar mitotic but absence proliferation. our experiments, led hypertrophy with nuclear anaplasia, part through endoreduplication. Oncogene-induced gene expression changes overlapped those polyploid cancer after chemotherapy, which potentially mediate tumor recurrence. Thus, provide useful aspects progression lack cellular
Language: Английский
Citations
0
Proceedings of the National Academy of Sciences, Journal Year: 2024, Volume and Issue: 121(39)
Published: Sept. 17, 2024
Mammalian Yes-associated protein (YAP) and transcriptional coactivator with PDZ-binding motif (TAZ) Drosophila Yorkie (Yki) are transcription cofactors of the highly conserved Hippo signaling pathway. It has been long assumed that YAP/TAZ/Yki drives cell proliferation during organ growth. However, its instructive role in regulating developmentally programmed growth, if any, remains elusive. Out-of-context gain often turns oncogenic. Paradoxically, mechanically strained, differentiated squamous epithelia display constitutive nuclear signaling. The unknown, therefore, is how a growth-promoting restricts epithelia. Here, we show reminiscent tumor suppressor, Yki negatively regulates growth–promoting PI3K/Akt/TOR tubular organs. Thus, downregulation epithelium adult male accessory gland (MAG) up-regulates signaling, inducing hypertrophy, exit from their cycle arrest, and, finally, culminating carcinoma (SCC). blocking arrests loss-induced MAG-SCC. Further, MAG-SCCs, like other lethal carcinomas, secrete cachectin, Impl2—the homolog mammalian IGFBP7—inducing cachexia shortening lifespan males. Moreover, organs, dorsal trunk larval tracheal airways or Malpighian tubules, triggers PI3K/Akt/TOR-induced hypertrophy. Our results reveal plays an instructive, antiproliferative
Language: Английский
Citations
1
bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2024, Volume and Issue: unknown
Published: May 12, 2024
Abstract Drosophila models for tumorigenesis and metastasis have revealed conserved mechanisms of signaling that are also involved in mammalian cancer. Many these use the proliferating tissues larval stages development, when highly mitotically active, or stem cells abundant. Fewer adult animals to initiate tumor formation many largely terminally differentiated postmitotic. The accessory glands prostate-like a model some aspects prostate using this tissue has been explored. In model, oncogenic was induced during proliferative stage gland raising question how activity would impact postmitotic tissue. Here, we show leads activation pro-tumorigenic program, similar observed mitotic tissues, but absence proliferation. Oncogenic hyperplasia with nuclear anaplasia aneuploidy through endoreduplication, which increases polyploidy occasionally results non-mitotic neoplastic-like extrusions. We compare gene expression changes our endocycling cancer by chemotherapy, potentially mediate recurrence after treatment. Similar pathways activated cells, suggesting provide useful progression do not involve cellular
Language: Английский
Citations
0
bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2024, Volume and Issue: unknown
Published: Aug. 13, 2024
Abstract The Drosophila Ejaculatory duct (ED) is a secretory tissue of the somatic male reproductive system. ED involved in secretion seminal fluid components and ED-specific antimicrobial peptides that aid fertility female post-mating response. composed epithelial cells surrounded by layer innervated contractile muscle. grows young adult males during first 24h post-eclosion, but cell cycle status role post-eclosion growth have been unexplored. Here, we show undergo variant cycles lacking mitosis called endocycle, lead to an increase organ size post eclosion. largely exit endocycle day 3 adulthood, when ceases, resulting containing ploidies ranging from 8C-32C. directly correlates with ploidy cells, additional ectopic endocycles increasing size. When endoreplication compromised it leads reduced size, protein synthesis fertility. We provide evidence endocycling dependent on Juvenile hormone (JH) signaling suggest hormone-induced early required for optimal function tissue. propose use as post-mitotic model study polyploidy regulating function.
Language: Английский
Citations
0
bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2024, Volume and Issue: unknown
Published: Aug. 26, 2024
The brain is an organ comprised mostly of long-lived, quiescent cells that perform vital functions throughout animal's life. Due to the brain's limited regenerative ability, these long-lived must engage unique mechanisms cope with accumulated damage over time. We have shown a subset differentiated neuronal and glial in fruit fly become polyploid during adulthood. Cell cycle re-entry has previously been associated neurodegeneration, but there may be more complex relationship between polyploidy cell fitness brain. Here, we examine how known lifespan modifiers influence accumulation aging Flies aged at low temperature, or protein diet, accumulate slowly than expected if this phenotype were solely regulated by mechanisms. Despite slower cells, animals under conditions extend eventually reach similar levels as controls. Our work suggests can timing adult brain, indicating flexible window plasticity
Language: Английский
Citations
0
Proceedings of the National Academy of Sciences, Journal Year: 2024, Volume and Issue: 121(44)
Published: Oct. 25, 2024
Sexual reproduction requires the choreographed interaction of female cells and molecules with sperm seminal fluid. In internally fertilizing animals, these interactions are managed by specialized tissues within reproductive tract (FRT), such as a uterus, glands, storage organs. However, somatic remain understudied, hindering insight into molecular that support fertility. Here, we report identification, characterization, analysis cell types throughout FRT in premier
Language: Английский
Citations
0
Biochemical Society Transactions, Journal Year: 2024, Volume and Issue: unknown
Published: Nov. 7, 2024
The growth and development of metazoan organisms is dependent upon a co-ordinated programme cellular proliferation differentiation, from the initial formation zygote through to maintenance mature organs in adult organisms. Early studies ex vivo cultures unicellular eukaryotes described cyclic nature cell division characterised by periods DNA synthesis (S-phase) segregation newly synthesized chromosomes (M-phase) interspersed seeming inactivity, gap phases, G1 G2. We now know that G2 play critical roles regulating cycle, including monitoring favourable environmental conditions facilitate division, ensuring genomic integrity prior replication nuclear division. M-phase usually followed physical separation nascent daughters, termed cytokinesis. These phases where leads S phase, M phase subsequent cytokinesis produce two both identical composition morphology are what might be an archetypal Studies many different species have demonstrated this stereotypical cycle often subverted specific developmental outcomes, examples over 100 years analysis Drosophila melanogaster uncovered modes within one species.
Language: Английский
Citations
0
Developmental Biology, Journal Year: 2024, Volume and Issue: unknown
Published: Dec. 1, 2024
Language: Английский
Citations
0