The process of resumption of the first meiotic division (RMI) in mammalian oocytes includes germinal vesicle breakdown (GVBD), spindle formation during first metaphase (MI), segregation of homologous chromosomes, extrusion of the first polar body (PBI) and an arrest at metaphase of the second meiotic division (MII). Previous studies suggest a role for Fyn, a non-receptor Src family tyrosine kinase, in the exit from MII arrest. In the current study we characterized the involvement of Fyn in RMI. Western blot analysis demonstrated a significant, proteasome independent, degradation of Fyn during GVBD. Immunostaining of fixed oocytes and confocal imaging of live oocytes microinjected with Fyn complementary RNA (cRNA) demonstrated Fyn localization to the oocyte cortex and to the spindle poles. Fyn was recruited during telophase to the cortical area surrounding the midzone of the spindle and was then translocated to the contractile ring during extrusion of PBI. GVBD, exit from MI and PBI extrusion were inhibited in oocytes exposed to the chemical inhibitor SU6656 or microinjected with dominant negative Fyn cRNA. None of the microinjected oocytes showed misaligned or lagging chromosomes during chromosomes segregation and the spindle migration and anchoring were not affected. However, the extruded PBI was of large size. Altogether, a role for Fyn in regulating several key pathways during the first meiotic division in mammalian oocytes is suggested, particularly at the GV and metaphase checkpoints and in signaling the ingression of the cleavage furrow.
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http://dx.doi.org/10.4161/cc.9.8.11299 | DOI Listing |
Proc Natl Acad Sci U S A
January 2025
Division of Biology and Biological Engineering, California Institute of Technology, Pasadena, CA 91125.
From RNA interference to chromatin silencing, diverse genome defense pathways silence selfish genetic elements to safeguard genome integrity. Despite their diversity, different defense pathways share a modular organization, where numerous specificity factors identify diverse targets and common effectors silence them. In the PIWI-interacting RNA (piRNA) pathway, target RNAs are first identified by complementary base pairing with piRNAs and then silenced by PIWI-clade nucleases.
View Article and Find Full Text PDFIn meiosis, one round of DNA replication followed by two rounds of chromosome segregation halves the ploidy of the original cell. Accurate chromosome segregation in meiosis I depends on recombination between homologous chromosomes. Sister centromeres attach to the same spindle pole in this division and only segregate in meiosis II.
View Article and Find Full Text PDFNatl Sci Rev
January 2025
State Key Laboratory of Cardiology and Medical Innovation Center, Department of Reproductive Medicine Center, Shanghai East Hospital, Frontier Science Center for Stem Cell Research, School of Life Sciences and Technology, Tongji University, Shanghai 200092, China.
The overactivation of transposable elements (TEs) is a significant threat to male reproduction, particularly during the delicate process of spermatogenesis. Here, we report that zinc finger protein ZCCHC8-a key component of the nuclear exosome targeting (NEXT) complex that is involved in ribonucleic acid (RNA) surveillance-is required for TE silencing during spermatogenesis. Loss of ZCCHC8 results in delayed meiotic progression and reduced production of round spermatids (RS).
View Article and Find Full Text PDFCytoskeleton (Hoboken)
January 2025
Department of Life Sciences, University of Siena, Siena, Italy.
We analysed here the dynamic of the kinesin-like Pavarotti (Pav) during male gametogenesis of wild-type and Sas4 mutant flies. Pav localizes to the equatorial region and the inner central spindle of late anaphase wild-type spermatogonia and displays a strong concentration at the midbody during late telophase. At metaphase of the first meiotic division, Pav shows widespread localization on the equatorial region of the spermatocytes.
View Article and Find Full Text PDFEMBO J
January 2025
Newcastle University Biosciences Institute (NUBI), Central Parkway, Newcastle University, NE1 3BZ, Newcastle upon Tyne, UK.
The cellular concentrations of splicing factors (SFs) are critical for controlling alternative splicing. Most serine and arginine-enriched (SR) protein SFs regulate their own concentration via a homeostatic feedback mechanism that involves regulation of inclusion of non-coding 'poison exons' (PEs) that target transcripts for nonsense-mediated decay. The importance of SR protein PE splicing during animal development is largely unknown despite PE ultra-conservation across animal genomes.
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