Honors & Awards
Highest honors for research internship, Department of Biology, Ecole Polytechnique (2007)
Doctoral Fellowship, Ecole Polytechnique (2007-2010)
Doctoral Fellowship, French Foundation for Medical Research (FRM) (2010-2011)
Ingenieur, Ecole Polytechnique (2007)
Master of Science, Ecole Polytechnique (2007)
Doctor of Philosophy, Universite De Paris Vi (2011)
Anne Villeneuve, Postdoctoral Faculty Sponsor
Manipulation of Karyotype in Caenorhabditis elegans Reveals Multiple Inputs Driving Pairwise Chromosome Synapsis During Meiosis.
2015; 201 (4): 1363-1379
Meiotic chromosome segregation requires pairwise association between homologs, stabilized by the synaptonemal complex (SC). Here, we investigate factors contributing to pairwise synapsis by investigating meiosis in polyploid worms. We devised a strategy, based on transient inhibition of cohesin function, to generate polyploid derivatives of virtually any Caenorhabditis elegans strain. We exploited this strategy to investigate the contribution of recombination to pairwise synapsis in tetraploid and triploid worms. In otherwise wild-type polyploids, chromosomes first sort into homolog groups, then multipartner interactions mature into exclusive pairwise associations. Pairwise synapsis associations still form in recombination-deficient tetraploids, confirming a propensity for synapsis to occur in a strictly pairwise manner. However, the transition from multipartner to pairwise association was perturbed in recombination-deficient triploids, implying a role for recombination in promoting this transition when three partners compete for synapsis. To evaluate the basis of synapsis partner preference, we generated polyploid worms heterozygous for normal sequence and rearranged chromosomes sharing the same pairing center (PC). Tetraploid worms had no detectable preference for identical partners, indicating that PC-adjacent homology drives partner choice in this context. In contrast, triploid worms exhibited a clear preference for identical partners, indicating that homology outside the PC region can influence partner choice. Together, our findings, suggest a two-phase model for C. elegans synapsis: an early phase, in which initial synapsis interactions are driven primarily by recombination-independent assessment of homology near PCs and by a propensity for pairwise SC assembly, and a later phase in which mature synaptic interactions are promoted by recombination.
View details for DOI 10.1534/genetics.115.182279
View details for PubMedID 26500263
- Manipulation of Karyotype in Caenorhabditis elegans Reveals Multiple Inputs Driving Pairwise Chromosome Synapsis During Meiosis GENETICS 2015; 201 (4): 1363-?
- DNA Helicase HIM-6/BLM Both Promotes MutS gamma-Dependent Crossovers and Antagonizes MutS gamma-Independent Interhomolog Associations During Caenorhabditis elegans Meiosis GENETICS 2014; 198 (1): 193-?
- Evidence That Masking of Synapsis Imperfections Counterbalances Quality Control to Promote Efficient Meiosis PLOS GENETICS 2013; 9 (12)
Live Imaging of Bicoid-Dependent Transcription in Drosophila Embryos
2013; 23 (21): 2135-2139
The early Drosophila embryo is an ideal model to understand the transcriptional regulation of well-defined patterns of gene expression in a developing organism. In this system, snapshots of transcription measurements obtained by RNA FISH on fixed samples cannot provide the temporal resolution needed to distinguish spatial heterogeneity from inherent noise. Here, we used the MS2-MCP system to visualize in living embryos nascent transcripts expressed from the canonical hunchback (hb) promoter under the control of Bicoid (Bcd). The hb-MS2 reporter is expressed as synchronously as endogenous hb in the anterior half of the embryo, but unlike hb it is also active in the posterior, though more heterogeneously and more transiently than in the anterior. The length and intensity of active transcription periods in the anterior are strongly reduced in absence of Bcd, whereas posterior ones are mostly Bcd independent. This posterior noisy signal decreases progressively through nuclear divisions, so that the MS2 reporter expression mimics the known anterior hb pattern at cellularization. We propose that the establishment of the hb pattern relies on Bcd-dependent lengthening of transcriptional activity periods in the anterior and may require two distinct repression mechanisms in the posterior.
View details for DOI 10.1016/j.cub.2013.08.053
View details for Web of Science ID 000326993600023
View details for PubMedID 24139736
The time to measure positional information: maternal Hunchback is required for the synchrony of the Bicoid transcriptional response at the onset of zygotic transcription
2010; 137 (16): 2795-2804
It is widely accepted that morphogenetic gradients determine cell identity by concentration-dependent activation of target genes. How precise is each step in the gene expression process that acts downstream of morphogens, however, remains unclear. The Bicoid morphogen is a transcription factor directly activating its target genes and provides thus a simple system to address this issue in a quantitative manner. Recent studies indicate that the Bicoid gradient is precisely established in Drosophila embryos after eight nuclear divisions (cycle 9) and that target protein expression is specified five divisions later (cycle 14), with a precision that corresponds to a relative difference of Bicoid concentration of 10%. To understand how such precision was achieved, we directly analyzed nascent transcripts of the hunchback target gene at their site of synthesis. Most anterior nuclei in cycle 11 interphasic embryos exhibit efficient biallelic transcription of hunchback and this synchronous expression is specified within a 10% difference of Bicoid concentration. The fast diffusion of Bcd-EGFP (7.7 mum(2)/s) that we captured by fluorescent correlation spectroscopy in the nucleus is consistent with this robust expression at cycle 11. However, given the interruption of transcription during mitosis, it remains too slow to be consistent with precise de novo reading of Bicoid concentration at each interphase, suggesting the existence of a memorization process that recalls this information from earlier cycles. The two anterior maternal morphogens, Bicoid and Hunchback, contribute differently to this early response: whereas Bicoid provides dose-dependent positional information along the axis, maternal Hunchback is required for the synchrony of the response and is therefore likely to be involved in this memorization process.
View details for DOI 10.1242/dev.051300
View details for Web of Science ID 000280339000019
View details for PubMedID 20663819