JNK signalling controls remodelling of the segment boundary through cell reprogramming during Drosophila morphogenesis.

Segments are fundamental units in animal development which are made of distinct cell lineages separated by boundaries. Although boundaries show limited plasticity during their formation for sharpening, cell lineages make compartments that become tightly restricted as development goes on. Here, we characterize a unique case of breaking of the segment boundary in late drosophila embryos. During dorsal closure, specific cells from anterior compartments cross the segment boundary and enter the adjacent posterior compartments. This cell mixing behaviour is driven by an anterior-to-posterior reprogramming mechanism involving de novo expression of the homeodomain protein Engrailed. Mixing is accompanied by stereotyped local cell intercalation, converting the segment boundary into a relaxation compartment important for tension-release during morphogenesis. This process of lineage switching and cell remodelling is controlled by JNK signalling. Our results reveal plasticity of segment boundaries during late morphogenesis and a role for JNK-dependent developmental reprogramming in this process.

Medical tourism for late abortion: Women's profile and circumstances. A quantitative study among women who travelled within Europe for late abortion.

BACKGROUND: In France, women seeking abortion must do so before the maximum legal limit of 12 weeks of pregnancy (14 Gestational Weeks). Women seeking abortion after the 12-week limit tend to travel to the Netherlands, where the maximum legal limit is 22 weeks of pregnancy. The purpose of this study was to identify the profile and circumstances of women who travel from France to the Netherlands for a late abortion. METHODS: A descriptive, monocentric study was conducted in a Dutch abortion clinic, where a standardized, anonymous questionnaire was administered to women from France, holding an appointment for late abortion. Data was collected from July 2020 to December 2020. Data analysis was performed with R 4.0.3 software. RESULTS: Thirty-seven women participated in the study. Most of the women were young (15-25 y. o.), without any prior pregnancy, single, in paid employment, with an educational level less than or equal to a high school degree. Most of the women had regular gynaecological follow-up, used contraception, mostly birth control pills, and had already discussed emergency contraception or abortion with a healthcare professional. The women had delayed awareness of their pregnancy and visited the clinic at 18 weeks of pregnancy or later, beyond the 12-week French legal limit for abortion. CONCLUSION: Risk factors likely to lead to medical tourism for late abortion include young age (15-25 y. o.), first pregnancy, being insufficiently informed about available contraceptive methods.

Participation rate in cervical cancer screening in general practice related to the proximity of gynecology care facilities: A 3 year follow-up cohort study.

Cervical cancer screening (CCS) by Pap tests is mainly performed by gynecologists in France, but also by general practitioners (GPs) and midwives. The screening uptake is insufficient to reduce the incidence of cervical neoplasms. Our aim was to investigate the association between screening rates in patients listed with GPs and the distance between GPs' offices and gynecology facilities. The population of 345 GPs, and their 93,918 female patients eligible for screening over 3 years (2013-2015), were derived from the Health Insurance claim database. We estimated the socioeconomic level of the geographical area of GPs' offices using the European Deprivation Index (EDI). The proximity of gynecology facilities was calculated by computing their distance from GPs' offices (in order to adjust the proximity of gynecology facilities with EDI and performance of smears by the GP). The number of gynecologists within 5 km of a GP's office was associated with the CCS rate increasing by 0.31% for every unit increase in the density of gynecologists within 5 km (p < 0.0001). The close proximity of gynecology facilities was not significantly associated with screening uptake among female patients when the office of the GP where they were registered was settled in a deprived area.

A mathematical model for dorsal closure.

During embryogenesis, drosophila embryos undergo epithelial folding and unfolding, which leads to a hole in the dorsal epidermis, transiently covered by an extraembryonic tissue called the amnioserosa. Dorsal closure (DC) consists of the migration of lateral epidermis towards the midline, covering the amnioserosa. It has been extensively studied since numerous physical mechanisms and signaling pathways present in DC are conserved in other morphogenetic events and wound healing in many other species (including vertebrates). We present here a simple mathematical model for DC that involves a reduced number of parameters directly linked to the intensity of the forces in the presence and which is applicable to a wide range of geometries of the leading edge (LE). This model is a natural generalization of the very interesting model proposed in Hutson et al. (2003). Being based on an ordinary differential equation (ODE) approach, the previous model had the advantage of being even simpler, but this restricted significantly the variety of geometries that could be considered and thus the number of modified dorsal closures that could be studied. A partial differential equation (PDE) approach, as the one developed here, allows considering much more general situations that show up in genetically or physically perturbed embryos and whose study will be essential for a proper understanding of the different components of the DC process. Even for native embryos, our model has the advantage of being applicable since an early stages of DC when there is no antero-posterior symmetry (approximately verified only in the late phases of DC). We validate our model in a native setting and also test it further in embryos where the zipping force is perturbed through the expression of spastin (a microtubule severing protein). We obtain variations of the force coefficients that are consistent with what was previously described for this setting.

The association between cervical cancer screening participation and the deprivation index of the location of the family doctor's office.

BACKGROUND: Cervical cancer screening rates are known to be strongly associated with socioeconomic status. Our objective was to assess whether the rate is also associated with an aggregated deprivation marker, defined by the location of family doctors' offices. METHODS: To access this association, we 1) collected data from the claim database of the French Health Insurance Fund about the registered family doctors and their enlisted female patients eligible for cervical screening; 2) carried out a telephone survey with all registered doctors to establish if they were carrying out Pap-smears in their practices; 3) geotracked all the doctors' offices in the smallest existing blocks of socioeconomic homogenous populations (IRIS census units) that were assigned a census derived marker of deprivation, the European Deprivation Index (EDI), and a binary variable of urbanization; and 4) we used a multivariable linear mixed model with IRIS as a random effect. RESULTS: Of 348 eligible doctors, 343 responded to the telephone survey (98.6%) and were included in the analysis, encompassing 88,152 female enlisted patients aged 25-65 years old. In the multivariable analysis (adjusted by the gender of the family doctor, the practice of Pap-smears by the doctor and the urbanization of the office location), the EDI of the doctor's office was strongly associated with the cervical cancer screening participation rate of eligible patients (p<0.001). CONCLUSION: The EDI linked to the location of the family doctor's office seems to be a robust marker to predict female patients' participation in cervical cancer screening.

PTEN controls junction lengthening and stability during cell rearrangement in epithelial tissue.

Planar cell rearrangements control epithelial tissue morphogenesis and cellular pattern formation. They lead to the formation of new junctions whose length and stability determine the cellular pattern of tissues. Here, we show that during Drosophila wing development the loss of the tumor suppressor PTEN disrupts cell rearrangements by preventing the lengthening of newly formed junctions that become unstable and keep on rearranging. We demonstrate that the failure to lengthen and to stabilize is caused by the lack of a decrease of Myosin II and Rho-kinase concentration at the newly formed junctions. This defect results in a heterogeneous cortical contractility at cell junctions that disrupts regular hexagonal pattern formation. By identifying PTEN as a specific regulator of junction lengthening and stability, our results uncover how a homogenous distribution of cortical contractility along the cell cortex is restored during cell rearrangement to control the formation of epithelial cellular pattern.

Evolutionary conservation of early mesoderm specification by mechanotransduction in Bilateria.

The modulation of developmental biochemical pathways by mechanical cues is an emerging feature of animal development, but its evolutionary origins have not been explored. Here we show that a common mechanosensitive pathway involving ß-catenin specifies early mesodermal identity at gastrulation in zebrafish and Drosophila. Mechanical strains developed by zebrafish epiboly and Drosophila mesoderm invagination trigger the phosphorylation of ß-catenin-tyrosine-667. This leads to the release of ß-catenin into the cytoplasm and nucleus, where it triggers and maintains, respectively, the expression of zebrafish brachyury orthologue notail and of Drosophila Twist, both crucial transcription factors for early mesoderm identity. The role of the ß-catenin mechanosensitive pathway in mesoderm identity has been conserved over the large evolutionary distance separating zebrafish and Drosophila. This suggests mesoderm mechanical induction dating back to at least the last bilaterian common ancestor more than 570 million years ago, the period during which mesoderm is thought to have emerged.

Mechanical induction in embryonic development and tumor growth integrative cues through molecular to multicellular interplay and evolutionary perspectives.

Embryonic development is a coordination of multicellular biochemical patterning and morphogenetic movements. Last decades revealed the close control of myosin-II-dependent biomechanical morphogenesis by patterning gene expression, with constant progress in the understanding of the underlying molecular mechanisms. Reversed control of developmental gene expression and of myosin-II patterning by the mechanical strains developed by morphogenetic movements was recently revealed at Drosophila gastrulation, through mechanotransduction processes involving the Armadillo/beta-catenin and the downstream of Fog Rho pathways. Here, we present the theoretical (simulations integrating the accumulated knowledge in the genetics of early embryonic development and morphogenesis) and the experimental (genetic and biophysical control of morphogenetic movements) tools having allowed the uncoupling of pure genetic inputs from pure mechanical inputs in the regulation of gene expression and myosin-II patterning. Specifically, we describe the innovative magnetic tweezers tools we have set up to measure and apply physiological strains and forces in vivo, from the inside of the tissue, to modulate and mimic morphogenetic movements in living embryos. We discuss mechanical induction incidence in tumor development and perspective in evolution.