A non-canonical role of somatic CYCLIN D/CYD-1 in oogenesis and reproductive aging, dependent on the FOXO/DAF-16 activation state

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

Published: Dec. 11, 2023

Abstract For the optimal survival of a species, an organism coordinates its reproductive decisions with nutrient availability niche. Thus, nutrient-sensing pathways like insulin-IGF-1 signaling (IIS) play important role in modulating cell division, oogenesis, and aging. Lowering IIS leads to activation downstream FOXO transcription factor (TF) DAF-16 Caenorhabditis elegans which promotes oocyte quality delays However, less is known about how axis responds changes cycle proteins, particularly somatic tissues. Here, we show new aspect regulation germline by this nutrient- sensing axis. First, that canonical G1-S cyclin, cyclin D / cyd-1 , regulates aging from uterine tissue wild-type worms. Then, knocking down receptor mutant arrests oogenesis at pachytene stage meiosis-1 FOXO/DAF-16-dependent manner. We find activated FOXO/DAF-16 destroys gonad tissues sheath cells, transcriptionally prevents spermatogenesis-to- switch orchestrate arrest. Deleting releases arrest restores but production poor-quality oocytes. Together, our study reveals unrecognized non-autonomous interaction CYD-1 oogenesis.

Language: Английский

Formation of Benign Tumours by Stem Cell Misregulation

Published: Jan. 10, 2022

Our tissues usually have just the right number of cells to optimally fulfil their function. Not enough within a tissue can lead dysfunction, while too many result in tumour. Yet, how this homeostatic balance is maintained remains poorly defined. Most differentiated finite lifespan and need be replaced at corresponding pace maintain homeostasis. These new are generated by proliferation stem/progenitor that serve tissue. Work simple invertebrates clearly suggests stem respond least two types signals: niche signaling growth factors. Niche signals promote undifferentiated state preventing differentiation, thus allow for cell self-renewal. Growth factor sources comprise systemic input reflecting animal’s nutritional status, localized, feedback from serve. That signal couples rates tissue’s cells. Evidence organisms benign tumours arise deregulation either or signaling. Namely, constitutive promotes formation “stem cell” tumours, defective leads tumours. We propose these principles may conserved underlie tumour humans, evolve into cancer.

Language: Английский

Sensory neurons safeguard from mutational inheritance by controlling the CEP-1/p53-mediated DNA damage response in primordial germ cells

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2022, Volume and Issue: unknown

Published: July 20, 2022

Abstract The genome integrity control in primordial germ cells (PGCs) is prerequisite for the inheritance of stable genomes. PGCs C. elegans are embedded a somatic niche that regulates its DNA damage response (DDR). Here, we show AMPK-like kinases KIN-29 and AAK-2 required arresting carrying persistent damage. We determined ASI neurons, which sense environmental conditions such as nutrient availability, secrete TGF-beta-like ligand DAF-7 recognized by DAF-1 receptor PGCs. ASI-dependent signaling induction CEP-1/p53 amid Using single worm whole sequencing, establish defective CEP-1/p53-regulated DDR ultimately results de novo germline mutations. Our indicate sensory neurons safeguard from mutations suggesting possibility perception environment could direct genetic inheritance. One sentence summary regulate CEP-1/p53-dependent via TGF-beta influence inherited mutational burden.

Language: Английский