Biology subjects

Monteiro, V. L.

Publications and source records attributed to Monteiro, V. L..

3 recordsLinked to original sources

bioRxiv2026

Ataxin-2 regulates the synaptonemal complex to ensure chromosome pairing during female meiosis

Sexual reproduction relies on meiotic recombination and the accurate segregation of homologous chromosomes to generate viable, genetically diverse gametes. While the molecular mechanisms of recombination and chromosome segregation are well studied, the upstream regulatory cues that drive expression of key meiotic genes remain poorly understood, especially in metazoans. Emerging evidence suggests that post-transcriptional regulation plays a central role in initiating and coordinating the meiotic program in both fruit flies and mammals. Here, we identify the RNA-binding protein Ataxin-2 (Atx2) as a crucial regulator of meiosis in Drosophila melanogaster. We show that Atx2 positively regulates meiotic factors, especially components of the synaptonemal complex (SC), a structure essential for pairing, recombination and segregation of homologous chromosomes. In Atx2-depleted germ cells, SC component mRNA and protein levels are markedly reduced, leading to defective SC assembly and maintenance. Consequently, homologous chromosomes fail to pair properly, which is essential to ensure homolog segregation and prevent aneuploidy. These findings uncover Atx2 as a key regulator of the SC and highlight an underappreciated layer of gene regulation essential for accurate meiotic chromosome segregation and fertility.

genetics↗

bioRxiv2025

TFAP2A+ embryonic progenitor cells undergo fate diversification to give rise to human amnion, germline, and mesoderm

Amnion, germline and mesoderm specification at the posterior end of the human embryo occur around the same time in vivo. Similarly, in vitro generation of germline and amnion is associated with mesoderm induction regardless of differentiation platform. Yet, the lineage relationships between amnion, germline and mesoderm remains unresolved. By adding Basement Membrane Extract (BME) to the media, we demonstrate emergence of TFAP2A+/SOX2-epithelial progenitor cells which develop in response to BMP receptor signaling. We track the order of embryonic events that take place from this progenitor pool revealing that amnion-like cells (AMLCs) and primordial germ cell (PGC)-like cells (PGCLCs) are specified first. Shortly after, gastrulating mesoderm-like cells (MeLCs) arise that undergo an epithelial to mesenchymal transition (EMT). These results highlight the interconnected role of basement membrane deposition and BMP receptor signaling in the specification of human germline, amnion and mesoderm from TFAP2A+ embryonic progenitors.

developmental biology↗

bioRxiv2025

Ataxin-2 preserves oocyte genome integrity by promoting timely premeiotic DNA replication

The faithful reassortment and transmission of chromosomes across generations is fundamental to species survival. While much is known about chromosome pairing and recombination, the upstream regulators controlling entry into the meiotic program remain largely elusive. In many species, including Drosophila and mammals, the decision to enter meiosis occurs prior to premeiotic DNA replication and is governed by post-transcriptional regulation, by yet to be discovered factors. Here, we identify the RNA-binding protein Ataxin-2 as a crucial and previously unrecognized regulator of meiotic entry. We show that Ataxin-2 acts post-transcriptionally to promote the entry into meiosis by downregulating the conserved cell cycle inhibitor Dacapo, the Drosophila ortholog of p21/p27. In the absence of Ataxin-2, germ cells mis-regulate Dacapo leading to delayed premeiotic DNA replication and sterility. Strikingly, when DNA replication is delayed and extends into the next stage of meiosis, synaptonemal complex formation, oocytes incur severe genomic DNA damage, likely caused by collisions between replication forks and the synaptonemal complex. Our findings establish Ataxin-2 as a pivotal factor in regulating premeiotic DNA replication and safeguarding oocyte genome stability, shedding new light on the intricate regulatory mechanisms that ensure successful meiosis and fertility.

genetics↗