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by claude@2026-07, 2026-07-03
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The study aimed to identify essential regulators of early zebrafish oogenesis by developing a long-term ovary culture system that supports physiological oocyte development ex vivo, then screening candidate regulators based on stage-specific oocyte transcriptomic data. Using genetics, pharmacological manipulations, and rescue experiments, the authors found that an mTOR–Stat3–Stathmin signaling pathway controls oocyte polarity by regulating centrosome behavior and microtubule organization, with mTOR acting upstream of Stat3. Loss of mTOR or Stat3 function and Stathmin overactivation caused aberrant centrosome regulation, microtubule destabilization, and dispersed mislocalized Buc condensates with loss of polarity; inhibition of Stathmin rescued cytoskeletal and polarity defects in stat3-/- or mTOR-deficient ovaries. The paper does not explicitly discuss endometriosis or adenomyosis; it was included in the corpus via a keyword match in the upstream search index.
Abstract
Summary In animals and plants, egg production is essential for fertility, reproduction, and embryonic development. The production of functional eggs in sufficient numbers for a female lifespan requires dynamic and precisely coordinated cellular and developmental programs in early oogenesis. However, our understanding of their underlying regulatory mechanisms is critically lacking. Here, we aimed to identify overlooked essential regulators of early oogenesis in zebrafish. First, we present the establishment of a long-term ovary culture system which enables physiological oocyte development from oogonia to primordial follicles in cultured ovaries, providing an invaluable ex-vivo platform for rapid investigation. Next, we utilized this system for robust functional screening of candidates from stage-specific oocyte transcriptomic data. We identified mTOR, Stat3, and Stathmin as novel regulators of oocyte polarity. By using a combination of genetics, pharmacological manipulations ex-vivo , and rescue experiments, we established an essential mTOR-Stat3-Stathmin pathway that orchestrates centrosome regulation and microtubule organization to facilitate oocyte polarity. Microtubules control the localization and condensation of the essential polarity regulator Bucky ball (Buc). Loss of mTOR or Stat3 functions, as well as overactivation of Stathmin (a microtubule destabilizing protein) resulted in aberrant centrosome regulation and destabilization of microtubules, leading to dispersed mis-localized Buc condensates and loss of polarity. We show that mTOR acts upstream of Stat3 in oocytes, and that inhibition of Stathmin in stat3 -/- or mTOR deficient ovaries rescued both cytoskeletal and polarity defects. We propose a novel mTOR-Stat3-Stathmin pathway which through cytoskeletal regulation, provides oocytes with polarization competence, a step likely widely conserved in biology. mTOR, Stat3, and Stathmin are known for their roles in cellular growth and cancer. Our work reveals their novel unpredicted functions in cell polarity during animal post-embryonic development.
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Summary
In animals and plants, egg production is essential for fertility, reproduction, and embryonic development. The production of functional eggs in sufficient numbers for a female lifespan requires dynamic and precisely coordinated cellular and developmental programs in early oogenesis. However, our understanding of their underlying regulatory mechanisms is critically lacking. Here, we aimed to identify overlooked essential regulators of early oogenesis in zebrafish. First, we present the establishment of a long-term ovary culture system which enables physiological oocyte development from oogonia to primordial follicles in cultured ovaries, providing an invaluable ex-vivo platform for rapid investigation. Next, we utilized this system for robust functional screening of candidates from stage-specific oocyte transcriptomic data. We identified mTOR, Stat3, and Stathmin as novel regulators of oocyte polarity. By using a combination of genetics, pharmacological manipulations ex-vivo, and rescue experiments, we established an essential mTOR-Stat3-Stathmin pathway that orchestrates centrosome regulation and microtubule organization to facilitate oocyte polarity. Microtubules control the localization and condensation of the essential polarity regulator Bucky ball (Buc). Loss of mTOR or Stat3 functions, as well as overactivation of Stathmin (a microtubule destabilizing protein) resulted in aberrant centrosome regulation and destabilization of microtubules, leading to dispersed mis-localized Buc condensates and loss of polarity. We show that mTOR acts upstream of Stat3 in oocytes, and that inhibition of Stathmin in stat3-/-or mTOR deficient ovaries rescued both cytoskeletal and polarity defects. We propose a novel mTOR-Stat3-Stathmin pathway which through cytoskeletal regulation, provides oocytes with polarization competence, a step likely widely conserved in biology. mTOR, Stat3, and Stathmin are known for their roles in cellular growth and cancer. Our work reveals their novel unpredicted functions in cell polarity during animal post-embryonic development.
Competing Interest Statement
The authors have declared no competing interest.
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