Fusome as a Cell-Cell Communication Channel of Drosophila Ovarian Cyst

In most animal species, female and male gametes are produced within clusters of germ cells which share a common cytoplasm through cell-cell channels. In Drosophila ovaries, these cells synchronise their divisions and specialise one cell of the cluster as the future egg. Both processes are organised by a germline-specific organelle of communication called the fusome. Until recently, the fusome has remained largely mysterious despite a hundred years of research on its composition, formation and functions. Novel results have now suggested several molecular mechanisms to explain how the fusome synchronises the divisions by controlling cell-cycle regulators and how it determines and polarises the future egg by organising the microtubule cytoskeleton. Importantly, a structure similar to the fusome has been identified during Xenopus oogenesis, suggesting that it is widely conserved from invertebrates to vertebrates, and that it thus serves an essential function

The origin of asymmetry : early polarisation of the Drosophila germline cyst and oocyte.

The anterior-posterior axis of Drosophila is established before fertilisation when the oocyte becomes polarised to direct the localisation of bicoid and oskarmRNAs to opposite poles of the egg. Here we review recent results that reveal that the oocyte acquires polarity much earlier than previously thought, at the time when it acquires its fate. The oocyte arises from a 16 cell germline cyst, and its selection and the initial cue for its polarisation are controlled by the asymmetric segregation of a germline specific organelle called the fusome. Several different downstream pathways then interpret this asymmetry to restrict distinct aspects of oocyte identity to this cell. Mutations in any of the 6 conserved PAR proteins disrupt the early polarisation of the oocyte and lead to a failure to maintain its identity. Surprisingly, mutations affecting the control of the mitotic or meiotic cell cycle also lead to a failure to maintain the oocyte fate, indicating crosstalk between the nuclear and cytoplasmic events of oocyte differentiation. The early polarity of the oocyte initiates a series of reciprocal signalling events between the oocyte and the somatic follicle cells that lead to a reversal of oocyte polarity later in oogenesis, which defines the anterior-posterior axis of the embryo

Évolution et développement des cellules germinales / Evolution and development of germ cells

Recherche Pages web : https://www.college-de-france.fr/site/en-cirb/huynh.htm et http://germcells.fr. Publication Clémot M., Molla-Herman A., Mathieu J., Huynh J.-R. et Dostatni N., « The replicative histone chaperone CAF1 is essential for the maintenance of identity and genome integrity in adult stem cells », Development, vol. 145, no 17, 2018, DOI : 10.1242/dev.161190

Integrin-independent repression of cadherin transcription by talin during axis formation in Drosophila.

The Drosophila melanogaster anterior–posterior axis becomes polarized early during oogenesis by the posterior localization of the oocyte within the egg chamber. The invariant position of the oocyte is thought to be driven by an upregulation of the adhesion molecule DE-cadherin in the oocyte and the posterior somatic follicle cells, providing the first in vivo example of cell sorting that is specified by quantitative differences in cell–cell adhesion. However, it has remained unclear how DE-cadherin levels are regulated. Here, we show that talin, known for its role in linking integrins to the actin cytoskeleton, has the unexpected function of specifically inhibiting Decadherin transcription. Follicle cells that are mutant for talin show a strikingly high level of DE-cadherin, due to elevated transcription of DE-cadherin. We demonstrate that this deregulation of DE-cadherin is sufficient to attract the oocyte to lateral and anterior positions. Surprisingly, this function of talin is independent of integrins. These results uncover a new role for talin in regulating cadherin-mediated cell adhesion

Development of the PSYCHS: Positive SYmptoms and Diagnostic Criteria for the CAARMS Harmonized with the SIPS

Aim: To harmonize two ascertainment and severity rating instruments commonly used for the clinical high risk syndrome for psychosis (CHR-P): the Structured Interview for Psychosis-risk Syndromes (SIPS) and the Comprehensive Assessment of At-Risk Mental States (CAARMS). Methods: The initial workshop is described in the companion report from Addington et al. After the workshop, lead experts for each instrument continued harmonizing attenuated positive symptoms and criteria for psychosis and CHR-P through an intensive series of joint videoconferences. Results: Full harmonization was achieved for attenuated positive symptom ratings and psychosis criteria, and modest harmonization for CHR-P criteria. The semi-structured interview, named Positive SYmptoms and Diagnostic Criteria for the CAARMS Harmonized with the SIPS (PSYCHS), generates CHR-P criteria and severity scores for both CAARMS and SIPS. Conclusions: Using the PSYCHS for CHR-P ascertainment, conversion determination, and attenuated positive symptom severity rating will help in comparing findings across studies and in meta-analyses

May Measurement Month 2018: a pragmatic global screening campaign to raise awareness of blood pressure by the International Society of Hypertension

Aims Raised blood pressure (BP) is the biggest contributor to mortality and disease burden worldwide and fewer than half of those with hypertension are aware of it. May Measurement Month (MMM) is a global campaign set up in 2017, to raise awareness of high BP and as a pragmatic solution to a lack of formal screening worldwide. The 2018 campaign was expanded, aiming to include more participants and countries. Methods and results Eighty-nine countries participated in MMM 2018. Volunteers (≥18 years) were recruited through opportunistic sampling at a variety of screening sites. Each participant had three BP measurements and completed a questionnaire on demographic, lifestyle, and environmental factors. Hypertension was defined as a systolic BP ≥140 mmHg or diastolic BP ≥90 mmHg, or taking antihypertensive medication. In total, 74.9% of screenees provided three BP readings. Multiple imputation using chained equations was used to impute missing readings. 1 504 963 individuals (mean age 45.3 years; 52.4% female) were screened. After multiple imputation, 502 079 (33.4%) individuals had hypertension, of whom 59.5% were aware of their diagnosis and 55.3% were taking antihypertensive medication. Of those on medication, 60.0% were controlled and of all hypertensives, 33.2% were controlled. We detected 224 285 individuals with untreated hypertension and 111 214 individuals with inadequately treated (systolic BP ≥ 140 mmHg or diastolic BP ≥ 90 mmHg) hypertension. Conclusion May Measurement Month expanded significantly compared with 2017, including more participants in more countries. The campaign identified over 335 000 adults with untreated or inadequately treated hypertension. In the absence of systematic screening programmes, MMM was effective at raising awareness at least among these individuals at risk

Évolution et développement des cellules germinales / Evolution and development of germ cells

    Responsable : Jean-René Huynh Germ cells are the only cells, which are transmitted from one generation to the next and can be considered immortal. Germ cells produce highly specialized cells, called gametes, which carry the genetic and cytoplasmic information defining a given species and which can initiate the formation of an entire organism. Understanding how germ cells develop is not only of paramount medical interest for reproductive medicine, but is also crucial to comprehend how anim..

Polarité cellulaire et détermination de l’ovocyte chez Drosophila melanogaster

Au cours de l'ovogenèse précoce, une seule cellule parmi un cyste de 16 cellules germinales est sélectionnée pour devenir un ovocyte. Des données récentes suggèrent que le choix de l’ovocyte est fortement biaisé dès la formation du cyste lui-même. Cependant, il a été aussi montré que, bien que sélectionné, l’identité de l’ovocyte a besoin d’être maintenue. Ce maintien de l’identité de l’ovocyte nécessite l’activité des homologues des gènes pur, d’abord identifiés chez Caenorhabditis elegans. Ces gènes par sont nécessaires pour établir la première polarisation de l’ovocyte, dès la région 3 du germarium. Ceci démontre une étonnante conservation entre la polarisation selon l’axe antéropostérieur de l’embryon unicellulaire de Caenorhabditis elegans et de l’ovocyte de Drosophile

[Regulation of germline stem cells: the niche expands in Drosophila]

International audienceOur fascination for stem cells originates from their ability to divide asymmetrically in order to self-renew and produce daughter cells which can differentiate and replenish tissues. Stem cells could thus represent an unlimited source of differentiated cells that could be used to repair malformed, damaged or ageing tissues. Understanding how their behaviour is regulated is then of paramount medical interest. Specific microenvironments surrounding the stem cells, termed "niches", were proposed to play a major role in the balance between self-renewal and differentiation. However, it is only recently, in the case of the stem cells producing the germline (GSGs) in Drosophila, that the cells and signals creating a niche were identified for the first time. Here, we review how this niche has been defined at the cellular and functional levels in vivo, thanks to the powerful genetic tools available in Drosophila. Such studies have revealed adhesive interactions, cell-cycle modifications and intercellular signals that control the GSC behavior. Extracellular signals from the niche activate the BMP or JAK-STAT pathways in the GSCs and are necessary for their maintenance. Strikingly, both signaling pathways are also sufficient to convert differentiated germ cells into functional GSCs, demonstrating in vivo that a niche has the capacity to regenerate stem cells from differentiated cells. Rapid progresses have further identified direct links between these signaling pathways and the transcriptional regulation of the GSCs, providing a simple paradigm for stem cells regulation. Many of these features and signals are conserved in stem cells niches from Drosophila to mammals. We can thus hope that research on the GSCs in Drosophila will benefit therapeutic approaches to human degenerative diseases