Cell Cycle Regulators in Female Meiosis of Drosophila melanogaster

Meiosis is a highly regulated and complex variation on the canonical cell cycle. It depends on the activity of most of the known mitotic cell cycle regulators, as well as many meiosis-specific factors that interact with and modify the activities of this core cell cycle machinery. This review will examine the roles of known mitotic cell cycle regulators and meiosis-specific factors in Drosophila female meiosis, focusing on three important meiotic events: nuclear envelope breakdown or maturation, establishment of the meiosis I spindle, and release from metaphase I arrest at ovulation. Many meiotic processes are controlled by the mitotic kinase, Cdk1 with its cyclin partners, cyclins A, B, and B3. Other major mitotic kinases, including Polo and Aurora B have been found to play multiple roles in Drosophila meiosis. The Anaphase Promoting Complex or Cyclosome (APC/C) controls many meiotic processes through regulation of Cdk1, the sister chromatid cohesion regulator, Separase and other targets. This review will focus on these and other meiotic regulators, emphasizing some of the technical advances that have driven the field forward in recent years, and highlighting gaps that need to be filled to achieve a more complete picture of how meiosis is regulated in Drosophila

Role of Securin, Separase and Cohesins in female meiosis and polar body formation in Drosophila

Chromosome segregation in meiosis is controlled by a conserved pathway that culminates in Separase-mediated cleavage of the α-kleisin Rec8, leading to dissolution of cohesin rings. Drosophila has no gene encoding Rec8, and the absence of a known Separase target raises the question of whether Separase and its regulator Securin (Pim in Drosophila) are important in Drosophila meiosis. Here, we investigate the role of Securin, Separase and the cohesin complex in female meiosis using fluorescence in situ hybridization against centromeric and arm-specific sequences to monitor cohesion. We show that Securin destruction and Separase activity are required for timely release of arm cohesion in anaphase I and centromere-proximal cohesion in anaphase II. They are also required for release of arm cohesion on polar body chromosomes. Cohesion on polar body chromosomes depends on the cohesin components SMC3 and the mitotic α-kleisin Rad21 (also called Vtd in Drosophila). We provide cytological evidence that SMC3 is required for arm cohesion in female meiosis, whereas Rad21, in agreement with recent findings, is not. We conclude that in Drosophila meiosis, cohesion is regulated by a conserved Securin–Separase pathway that targets a diverged Separase target, possibly within the cohesin complex

Study of Production and Adaptation Characters of Some Newly Obtained Genotypes of Durum Wheat (Triticum Durum Desf.) in Sub-Humid Region (El Harrouch North-Eastern of Algeria)

The experiment was carried out at DAOUDI Larbi pilot farm in El Harrouch, during the 2021/2022 crop year, under sub-humid weather conditions. The main objective of this research is based on the study of production and adaptation characters of seven durum wheat newly obtained genotypes (Triticum durum Desf.). The results of descriptive sheets according to UPOV recommendations (2014-2017), showed diversity between the varieties studied, such as: plant height, straw section, awns (presence, disposition, anthocyanin pigmentation, color, and length), ear (density, color, shape, length and glaucescence), lower glume (shape, color, weight and shape of shoulder, length and curvature of beak), neck glaucescence, length of rachis… According to the results obtained of production and adaptation characters we find that Numidia presented the high value of number of Plant/m2 (350 ± 4.58), Emilio Lepido showed a high level of Number of Herbaceous tillers/Plant (2.70 ± 0.52), number of Grains/Ear (37.1 ± 6.85), and Harvest index (35.62 Qunitals/Acres). While, the number of Ears tillering/Plant, number of Ears/m2, thousand grains weight, grain yield, biomass aerial, and economic yield (1.67 ± 0.31, 423.33 ± 15.95, 48.6 g, 62.13 ± 2.34 Qunitals/Acres, 184.6 ± 1.7 Qunitals/Acres and 98.88 ± 2.01 Qunitals/Acres). According to the results obtained the Shannon and Weaver relative diversity index showed a low diversity in all accessions studied (H’Mean=0.41). Finally, we concluded that the creation of descriptive sheets, the knowledge of production and adaptation parameters are considered as precursors of high yield, they allow us to better exploit these species according to economic needs, agro-ecological conditions, and mastery of production techniques in improvement programs

Distinct and Overlapping Requirements for Cyclins A, B, and B3 in \u3ci\u3eDrosophila\u3c/i\u3e Female Meiosis

Meiosis, like mitosis, depends on the activity of the cyclin dependent kinase Cdk1 and its cyclin partners. Here, we examine the specific requirements for the three mitotic cyclins, A, B, and B3 in meiosis of Drosophila melanogaster. We find that all three cyclins contribute redundantly to nuclear envelope breakdown, though cyclin A appears to make the most important individual contribution. Cyclin A is also required for biorientation of homologs in meiosis I. Cyclin B3, as previously reported, is required for anaphase progression in meiosis I and in meiosis II. We find that it also plays a redundant role, with cyclin A, in preventing DNA replication during meiosis. Cyclin B is required for maintenance of the metaphase I arrest in mature oocytes, for spindle organization, and for timely progression through the second meiotic division. It is also essential for polar body formation at the completion of meiosis. With the exception of its redundant role in meiotic maturation, cyclin B appears to function independently of cyclins A and B3 through most of meiosis. We conclude that the three mitotic cyclin-Cdk complexes have distinct and overlapping functions in Drosophila female meiosis

Rôle du facteur de transcription E2f1 dans la fonction et l’identité de la cellule bêta pancréatique et identification des mécanismes moléculaires

Type 2 Diabetes (T2D) is one of the most prevalent diseases in modern society, with more than 415 million people living with it. In recent years, treatments targeting Glucagon-Like Peptide 1 (GLP-1), a hormone secreted by entero-endocrine L-type cells, as well as its receptor agonists (GLP-1R), have been shown to be effective in restore normal blood glucose levels in diabetic patients.The laboratory has been interested for some years in the potential links existing between the regulators of the cell cycle and the metabolism, and in particular the protein E2F1. E2F1 has been shown to be an important regulator of metabolism with a role in adipose tissue, liver, muscle and pancreas.The GLP-1 pathway in the Beta cell (insulin secretory cell) and E2F1 signaling pathway have similar effects with a role on proliferation, anti-apoptotic and important effects in insulin secretion.From these observations, we investigated a potential link between E2F1 and the GLP-1 pathway within the pancreatic beta cell.Le Diabète de type 2 (DT2) est l’une des maladies les plus répandues dans la société moderne, avec plus de 415 millions de personnes atteintes. Ces dernières années, des traitements visant le Glucagon-Like Peptide 1 (GLP-1), hormone sécrétée par les cellules entéro-endocrines de type L, ainsi que des agonistes de son récepteur (GLP-1R), se sont avérés efficaces dans le rétablissement d’une glycémie normale de patients diabétiques.Le laboratoire s'intéresse depuis quelques années aux liens potentiels existant entre les régulateurs du cycle cellulaire et le métabolisme, et notamment la protéine E2F1. E2F1 a été montré comme un régulateurs important du métabolisme ayant un rôle dans le tissus adipeux, le foie, le muscle et le pancréas.La voie du GLP-1 dans la cellule Bêta (cellule sécrétrice d'insuline) et celle de E2F1 ont des effets similaires avec un rôle sur la prolifération de ces cellules, un rôle anti-apoptotique et des effets importants dans la sécrétion d'insuline.De ces observations, nous nous sommes intéressés à un lien potentiel entre E2F1 et la voie du GLP-1 au sein de la cellule bêta pancréatique

Role of the transcription factor E2f1 in pancreatic beta cell function and identity and identification of molecular mechanisms

Le Diabète de type 2 (DT2) est l’une des maladies les plus répandues dans la société moderne, avec plus de 415 millions de personnes atteintes. Ces dernières années, des traitements visant le Glucagon-Like Peptide 1 (GLP-1), hormone sécrétée par les cellules entéro-endocrines de type L, ainsi que des agonistes de son récepteur (GLP-1R), se sont avérés efficaces dans le rétablissement d’une glycémie normale de patients diabétiques.Le laboratoire s'intéresse depuis quelques années aux liens potentiels existant entre les régulateurs du cycle cellulaire et le métabolisme, et notamment la protéine E2F1. E2F1 a été montré comme un régulateurs important du métabolisme ayant un rôle dans le tissus adipeux, le foie, le muscle et le pancréas.La voie du GLP-1 dans la cellule Bêta (cellule sécrétrice d'insuline) et celle de E2F1 ont des effets similaires avec un rôle sur la prolifération de ces cellules, un rôle anti-apoptotique et des effets importants dans la sécrétion d'insuline.De ces observations, nous nous sommes intéressés à un lien potentiel entre E2F1 et la voie du GLP-1 au sein de la cellule bêta pancréatique.Type 2 Diabetes (T2D) is one of the most prevalent diseases in modern society, with more than 415 million people living with it. In recent years, treatments targeting Glucagon-Like Peptide 1 (GLP-1), a hormone secreted by entero-endocrine L-type cells, as well as its receptor agonists (GLP-1R), have been shown to be effective in restore normal blood glucose levels in diabetic patients.The laboratory has been interested for some years in the potential links existing between the regulators of the cell cycle and the metabolism, and in particular the protein E2F1. E2F1 has been shown to be an important regulator of metabolism with a role in adipose tissue, liver, muscle and pancreas.The GLP-1 pathway in the Beta cell (insulin secretory cell) and E2F1 signaling pathway have similar effects with a role on proliferation, anti-apoptotic and important effects in insulin secretion.From these observations, we investigated a potential link between E2F1 and the GLP-1 pathway within the pancreatic beta cell

Distinct and Overlapping Requirements for Cyclins A, B, and B3 in Drosophila Female Meiosis

Meiosis, like mitosis, depends on the activity of the cyclin dependent kinase Cdk1 and its cyclin partners. Here, we examine the specific requirements for the three mitotic cyclins, A, B, and B3 in meiosis of Drosophila melanogaster. We find that all three cyclins contribute redundantly to nuclear envelope breakdown, though cyclin A appears to make the most important individual contribution. Cyclin A is also required for biorientation of homologs in meiosis I. Cyclin B3, as previously reported, is required for anaphase progression in meiosis I and in meiosis II. We find that it also plays a redundant role, with cyclin A, in preventing DNA replication during meiosis. Cyclin B is required for maintenance of the metaphase I arrest in mature oocytes, for spindle organization, and for timely progression through the second meiotic division. It is also essential for polar body formation at the completion of meiosis. With the exception of its redundant role in meiotic maturation, cyclin B appears to function independently of cyclins A and B3 through most of meiosis. We conclude that the three mitotic cyclin-Cdk complexes have distinct and overlapping functions in Drosophila female meiosis

Cyclin B3 activates the Anaphase-Promoting Complex/Cyclosome in meiosis and mitosis.

In mitosis and meiosis, chromosome segregation is triggered by the Anaphase-Promoting Complex/Cyclosome (APC/C), a multi-subunit ubiquitin ligase that targets proteins for degradation, leading to the separation of chromatids. APC/C activation requires phosphorylation of its APC3 and APC1 subunits, which allows the APC/C to bind its co-activator Cdc20. The identity of the kinase(s) responsible for APC/C activation in vivo is unclear. Cyclin B3 (CycB3) is an activator of the Cyclin-Dependent Kinase 1 (Cdk1) that is required for meiotic anaphase in flies, worms and vertebrates. It has been hypothesized that CycB3-Cdk1 may be responsible for APC/C activation in meiosis but this remains to be determined. Using Drosophila, we found that mutations in CycB3 genetically enhance mutations in tws, which encodes the B55 regulatory subunit of Protein Phosphatase 2A (PP2A) known to promote mitotic exit. Females heterozygous for CycB3 and tws loss-of-function alleles lay embryos that arrest in mitotic metaphase in a maternal effect, indicating that CycB3 promotes anaphase in mitosis in addition to meiosis. This metaphase arrest is not due to the Spindle Assembly Checkpoint (SAC) because mutation of mad2 that inactivates the SAC does not rescue the development of embryos from CycB3-/+, tws-/+ females. Moreover, we found that CycB3 promotes APC/C activity and anaphase in cells in culture. We show that CycB3 physically associates with the APC/C, is required for phosphorylation of APC3, and promotes APC/C association with its Cdc20 co-activators Fizzy and Cortex. Our results strongly suggest that CycB3-Cdk1 directly activates the APC/C to promote anaphase in both meiosis and mitosis

Identification of PP2A-B55 targets uncovers regulation of emerin during nuclear envelope reassembly in Drosophila

Mitotic exit requires the dephosphorylation of many proteins whose phosphorylation was needed for mitosis. Protein phosphatase 2A with its B55 regulatory subunit (PP2A-B55) promotes this transition. However, the events and substrates that it regulates are incompletely understood. We used proteomic approaches in Drosophila to identify proteins that interact with and are dephosphorylated by PP2A-B55. Among several candidates, we identified emerin (otefin in Drosophila). Emerin resides in the inner nuclear membrane and interacts with the DNA-binding protein barrier-to-autointegration factor (BAF) via a LEM domain. We found that the phosphorylation of emerin at Ser50 and Ser54 near its LEM domain negatively regulates its association with BAF, lamin and additional emerin in mitosis. We show that dephosphorylation of emerin at these sites by PP2A-B55 determines the timing of nuclear envelope reformation. Genetic experiments indicate that this regulation is required during embryonic development. Phosphoregulation of the emerin–BAF complex formation by PP2A-B55 appears as a key event of mitotic exit that is likely conserved across species