A5055025945- Reproductive Biology and Fertility
- Sperm and Testicular Function
- CRISPR and Genetic Engineering
- DNA Repair Mechanisms
- Chromosomal and Genetic Variations
- RNA Research and Splicing
- Ovarian function and disorders
- Cancer-related molecular mechanisms research
- Renal and related cancers
- Carcinogens and Genotoxicity Assessment
- RNA modifications and cancer
- MicroRNA in disease regulation
- Particle accelerators and beam dynamics
- Particle Accelerators and Free-Electron Lasers
- Genetic and Clinical Aspects of Sex Determination and Chromosomal Abnormalities
- Acute Lymphoblastic Leukemia research
- Genomics and Chromatin Dynamics
- Prenatal Screening and Diagnostics
- RNA Interference and Gene Delivery
- Neuroendocrine regulation and behavior
- Developmental Biology and Gene Regulation
- Birth, Development, and Health
- Connective tissue disorders research
- Advanced biosensing and bioanalysis techniques
- Nuclear Structure and Function
European Molecular Biology Laboratory
2010-2024
GANIL
2023-2024
MRC Centre for Regenerative Medicine
2017
University of Edinburgh
2017
European Bioinformatics Institute
2017
European Molecular Biology Laboratory
2017
University of Rome Tor Vergata
2001-2015
Memorial Sloan Kettering Cancer Center
2005-2008
Albert Einstein College of Medicine
2005
Cornell University
2005
The process of erythropoiesis must be efficient and robust to supply the organism with red bloods cells both under condition homeostasis stress. microRNA (miRNA) pathway was recently shown regulate erythroid development. Here, we show that expression locus encoding miR-144 miR-451 is strictly dependent on Argonaute 2 required for homeostasis. Mice deficient miR-144/451 cluster display a cell autonomous impairment late erythroblast maturation, resulting in hyperplasia, splenomegaly, mild...
Abstract The gut microbiota operates at the interface of host–environment interactions to influence human homoeostasis and metabolic networks 1–4 . Environmental factors that unbalance microbial ecosystems can therefore shape physiological disease-associated responses across somatic tissues 5–9 However, systemic impact microbiome on germline—and consequently F 1 offspring it gives rise to—is unexplored 10 Here we show act as a key between paternal preconception environment intergenerational...
Defects in meiotic recombination many organisms result arrest because of activation a checkpoint(s). The proximal defect that triggers this checkpoint mammalian germ cells is not understood, but it has been suggested to involve either the presence DNA damage form unrepaired intermediates or defects homologous chromosome pairing and synapsis independent per se . To distinguish between these possibilities female line, we compared mouse oocyte development mutant fails double-strand breaks...
Fundamentally different recombination defects cause apoptosis of mouse spermatocytes at the same stage in development, IV seminiferous epithelium cycle, equivalent to mid-pachynema normal males. To understand cellular response(s) that triggers apoptosis, we examined markers spermatocyte development mice with defects. In Spo11(-)(/)(-) mutants, which lack double-strand breaks (DSBs) initiate recombination, express early mid-pachynema, forming chromatin domains contain sex body-associated...
Male fertility requires the continuous production of high quality motile spermatozoa in abundance. Alterations all three metrics cause oligoasthenoteratozoospermia, leading human sub/infertility. Post-mitotic spermatogenesis inclusive several meiotic stages and spermiogenesis (terminal differentiation) are transcriptionally inert, indicating potential importance for post-transcriptional microRNA (miRNA) gene-silencing pathway therein. We found expression miRNA generating enzyme Dicer within...
During meiosis in most sexually reproducing organisms, recombination forms crossovers between homologous maternal and paternal chromosomes thereby promotes proper chromosome segregation at the first meiotic division. The number distribution of are tightly controlled, but factors that contribute to this control poorly understood including mammals. Here we provide evidence ATM kinase or protein is essential for crossover formation mouse spermatocytes. deficiency causes multiple phenotypes...
Abstract Several developmental stages of spermatogenesis are transcriptionally quiescent which presents major challenges associated with the regulation gene expression. Here we identify that zygotene to pachytene transition is not only resumption transcription but also a wave programmed mRNA degradation essential for meiotic progression. We explored whether terminal uridydyl transferase 4- (TUT4-) or TUT7-mediated 3′ uridylation contributes this during pachynema. Indeed, both TUT4 and TUT7...
Repression of retrotransposons is essential for genome integrity and the development germ cells. Among retrotransposons, establishment CpG DNA methylation epigenetic silencing LINE1 (L1) elements intracisternal A particle (IAP) endogenous retrovirus (ERV) dependent upon piRNA pathway during embryonic cell reprogramming. Furthermore, Piwi protein Mili, guided by piRNAs, cleaves expressed L1 transcripts to post-transcriptionally enforce in meiotic The loss both Mili does not affect mitotic...
Overexpression of the TCL1 oncogene has been shown to play a causative role in T cell leukemias humans and mice. The characterization Tcl1 -deficient mice these studies indicates an important developmental for early embryogenesis. In wild-type embryos, is abundant first three mitotic cycles, during which it shuttles between nuclei embryo cortical regions cell-cycle-dependent fashion. absence this protein embryogenesis results reduced fertility female present elucidate mechanism responsible...
During the preovulatory period, cumulus cells (CCs) form a hyaluronan-protein extracellular matrix (cumulus expansion) that positively influences oocyte fertilization. Degradation of this and CC-oocyte complex (COC) dissociation occurs within few hours ovulation parallels aging oocytes. Modulation CC proteolytic activity by gonadotropins soluble factors has been hypothesized to determine such changes. In present study, we investigated plasminogen activator (PA) synthesis COCs during...
ABSTRACT In somatic cells, H2afx and Mdc1 are close functional partners in DNA repair damage response. However, it is not known whether they also involved the maintenance of genome integrity meiosis. By analyzing chromosome dynamics H2afx−/− spermatocytes, we found that synapsis autosomes X-Y chromosomes was impaired a fraction cells. Such defects correlated with an abnormal recombination profile. Conversely, dispensable for played only minor role synapsis, compared action H2afx. This...
Meiosis is the biological process that, after a cycle of DNA replication, halves cellular chromosome complement, leading to formation haploid gametes. Haploidization achieved via two successive rounds segregation, meiosis I and II. In mammals, during prophase I, homologous chromosomes align synapse through recombination-mediated mechanism initiated by introduction double-strand breaks (DSBs) SPO11 protein. male mice, if expression DSB number are reduced below heterozygosity levels, synapsis...
Abstract Female mammals achieve dosage compensation by inactivating one of their two X chromosomes during development, a process entirely dependent on Xist , an X-linked long non-coding RNA (lncRNA). At the onset chromosome inactivation (XCI), is up-regulated and spreads along future inactive chromosome. Contextually, it recruits repressive histone DNA modifiers that transcriptionally silence regulation tightly coupled to differentiation its expression under control both pluripotency...
Cumulus cells sustain the development and fertilization of mammalian oocyte. These are retained around oocyte by a hyaluronan-rich extracellular matrix synthesized before ovulation, process called cumulus cell-oocyte complex (COC) expansion. Hyaluronan release dispersion progressively occur after paralleling decline fertilization. We show here that, in mice, postovulatory changes temporally correlated to cell death. apoptosis disassembly also occurred ovulated COCs cultured vitro. expanded...
Abstract The medium energy beam transport of the SPIRAL2 superconducting linac contains a single bunch selection system equipped with 7.5 kW dump. This device, originally designed long flat slope to decrease power density so that maximum operating temperature was 170 °C, impacted by Coulomb scattering generating two side effects: heating downstream components and degrading current measurement uncertainty. paper relates way these problems were solved.
(Abstracted from Nature 2017;548:347–351) Gene expression in the early stages of zygotic development is characterized by a lack transcription and dependent on maternally deposited transcriptome. The competence mature oocyte, upon ovulation, to support fertilization largely defined maternal
Abstract In somatic cells, H2afx and Mdc1 are close functional partners in DNA repair damage response. However, it is not known whether they also involved the maintenance of genome integrity meiosis. By analyzing chromosome dynamics -/- spermatocytes, we found that synapsis autosomes X-Y chromosomes were impaired a relevant fraction cells. Such defect correlated with an abnormal recombination profile. Conversely, was dispensable for autosomes, only played minor role synapsis, relatively to ....