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Anbarci, D. N.

Publications and source records attributed to Anbarci, D. N..

4 recordsLinked to original sources

Maternal CENP-C restores centromere symmetry in mammalian zygotes to ensure proper chromosome segregation

Across metazoan species, the centromere-specific histone variant CENP-A is essential for accurate chromosome segregation, yet its regulation at the parental-to-zygote transition in mammals is poorly understood. To address this, we developed a CENP-A-mScarlet knock-in mouse model, which revealed sex-specific dynamics: mature sperm retains 10% of the CENP-A levels present in MII-oocytes. However, in zygotes prior to the first mitosis, this difference is resolved, using maternally inherited cytoplasmic-CENP-A. Notably, the increase in CENP-A at paternal centromeres is independent of sensing CENP-A asymmetry or the presence of maternal chromosomes. Instead, CENP-A equalization relies on asymmetric recruitment of maternal CENP-C to paternal centromeres. Depletion of maternal CENP-A decreases total CENP-A in pronuclei without disrupting equalization. In contrast, reducing maternal CENP-C or disruption of its dimerization domains impairs CENP-A equalization and chromosome segregation. Therefore, maternal CENP-C acts a key epigenetic regulator that resets centromeric symmetry at fertilization to preserve genome integrity. Highlights[bullet] CENP-A asymmetry between sperm and oocyte centromeres is a conserved feature from flies to mammals including mice and humans. [bullet]CENP-A asymmetry between parental centromeres is resolved prior to the first zygotic division via maternally inherited, cytoplasmic CENP-A. [bullet]Zygotic CENP-A levels in zygotes are regulated in a pronucleus-autonomous manner. [bullet]CENP-A equalization relies on asymmetric CENP-C recruitment to the paternal pronucleus and requires CENP-C dimerization. Key TermsCentromere; CENP-A; CENP-C; sperm; oocyte; zygote; intergenerational; epigenetics; mouse

genetics↗

Rediscovering the Rete Ovarii: a secreting auxiliary structure to the ovary

The rete ovarii (RO) is an appendage of the ovary that has been given little attention. Although the RO appears in drawings of the ovary in early versions of Grays Anatomy, it disappeared from recent textbooks, and is often dismissed as a functionless vestige in the adult ovary. Using PAX8 immunostaining and confocal microscopy, we characterized the fetal development of the RO in the context of the ovary. The RO consists of three distinct regions that persist in adult life, the intraovarian rete (IOR), the extraovarian rete (EOR), and the connecting rete (CR). While the cells of the IOR appear to form solid cords within the ovary, the EOR rapidly develops into a convoluted tubular epithelium ending in a distal dilated tip. Cells of the EOR are ciliated and exhibit cellular trafficking capabilities. The CR, connecting the EOR to the IOR, gradually acquires tubular epithelial characteristics by birth. Using microinjections into the distal dilated tip of the EOR, we found that luminal contents flow towards the ovary. Mass spectrometry revealed that the EOR lumen contains secreted proteins potentially important for ovarian function. We show that the cells of the EOR are closely associated with vasculature and macrophages, and are contacted by neuronal projections, consistent with a role as a sensory appendage of the ovary. The direct proximity of the RO to the ovary and its integration with the extraovarian landscape suggest that it plays an important role in ovary development and homeostasis.

developmental biology↗

Transcriptome analysis of the mouse fetal and adult rete ovarii and surrounding tissues

The rete ovarii (RO) is an epithelial structure that arises during fetal development in close proximity to the ovary and persists throughout adulthood in mice. However, the functional significance of the RO remains elusive, and it has been absent from recent discussions of female reproductive anatomy. The RO comprises three distinct regions: the intraovarian rete (IOR) within the ovary, the extraovarian rete (EOR) in the periovarian tissue, and the connecting rete (CR) linking the EOR and IOR. We hypothesize that the RO plays a pivotal role in maintaining ovarian homeostasis and responding to physiological changes. To uncover the nature and function of RO cells, we conducted transcriptome analysis, encompassing bulk, single-cell, and nucleus-level sequencing of both fetal and adult RO tissues using the Pax8-rtTA; Tre- H2B-GFP mouse line, where all RO regions express nuclear GFP. This study presents three datasets, which highlight RO-specific gene expression signatures and reveal differences in gene expression across the three RO regions during development and in adulthood. The integration and rigorous validation of these datasets will advance our understanding of the ROs roles in ovarian development, female maturation, and adult female fertility. Short narrativeThis study employs comprehensive bulk, single cell and single nucleus transcriptome analysis to uncover gene expression signatures of the fetal and adult rete ovarii (RO).

developmental biology↗

Integration of mouse ovary morphogenesis with developmental dynamics of the oviduct, ovarian ligaments, and rete ovarii.

Morphogenetic events during development of the fetal ovary are crucial to the establishment of female fertility. However, the effects of structural rearrangements of the ovary and surrounding reproductive tissues on ovary morphogenesis remain largely uncharacterized. Using tissue clearing and lightsheet microscopy, we found that ovary folding correlated with regionalization into cortex and medulla. Relocation of the oviduct to the ventral aspect of the ovary led to ovary encapsulation, and mutual attachment of the ovary and oviduct to the cranial suspensory ligament likely triggered ovary folding. Development of the rete ovarii correlated with events of ovary morphogenesis. Using genetic mouse models in which the oviduct and rete ovarii are perturbed, we found the oviduct is required for ovary encapsulation. This study reveals novel relationships among the ovary and surrounding tissues and paves the way for functional investigation of the relationship between architecture and differentiation of the mammalian ovary.

developmental biology↗