Depletion of Maternal Cyclin B3 Contributes to Zygotic Genome Activation in the Ciona Embryo

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Maternal and Zygotic Interactions between the Abnormal Oocyte Mutation and the Scute Inversion in DROSOPHILA MELANOGASTER

The authors have studied the interaction between the abnormal oocyte mutation and an inversion of the X chromosome, In( 1)sc⁴, which has a proximal breakpoint in or near the heterochromatic region (ABO) that maternally interacts with the abo product. It has been demonstrated that the presence of X chromosomes carrying this inversion, besides a marked increase in the severity of the maternal effect of the abo mutation, produces a zygotic effect resulting in the lethality of the progeny of stocks homozygous for abo and sc⁴. These results indicate that the sc⁴ inversion carries an abnormal region indispensable for the development of abo zygotes from sc⁴;abo mothers.     

Sexual Reproduction in Higher Plants Ⅰ: Fertilization and the Initiation of Zygotic Program

Sexual plant reproduction is a critical developmental step in the life cycle of higher plants, to allow maternal and paternal genes to be transmitted in a highly regulated manner to the next generation. During evolution, a whole set of signal transduction machinery is developed by plants to ensure an error-free recognition between male and female gametes and initiation of zygotic program. In the past few years, the molecular machineries underlying this biological process have been elucidated, particularly on the importance of synergid cells in pollen tube guidance, the Ca spike as the immediate response of fertilization and the epigenetic regulation of parental gene expressions in early zygotic embryogenesis. This review outlines the most recent development in this area.     

A Boolean Function for Neural Induction Reveals a Critical Role of Direct Intercellular Interactions in Patterning the Ectoderm of the Ascidian Embryo

A complex system of multiple signaling molecules often produce differential gene expression patterns in animal embryos. In the ascidian embryo, four signaling ligands, Ephrin-A.d (Efna.d), Fgf9/16/20, Admp, and Gdf1/3-r, coordinately induce Otx expression in the neural lineage at the 32-cell stage. However, it has not been determined whether differential inputs of all of these signaling pathways are really necessary. It is possible that differential activation of one of these signaling pathways is sufficient and the remaining signaling pathways are activated in all cells at similar levels. To address this question, we developed a parameter-free method for determining a Boolean function for Otx expression in the present study. We treated activities of signaling pathways as Boolean values, and we also took all possible patterns of signaling gradients into consideration. We successfully determined a Boolean function that explains Otx expression in the animal hemisphere of wild-type and morphant embryos at the 32-cell stage. This Boolean function was not inconsistent with three sensing patterns, which represented whether or not individual cells received sufficient amounts of the signaling molecules. These sensing patterns all indicated that differential expression of Otx in the neural lineage is primarily determined by Efna.d, but not by differential inputs of Fgf9/16/20, Admp, and Gdf1/3-r signaling. To confirm this hypothesis experimentally, we simultaneously knocked-down Admp, Gdf1/3-r, and Fgf9/16/20, and treated this triple morphant with recombinant bFGF and BMP4 proteins, which mimic Fgf9/16/20 and Admp/Gdf1/3-r activity, respectively. Although no differential inputs of Admp, Gdf1/3-r and Fgf9/16/20 signaling were expected under this experimental condition, Otx was expressed specifically in the neural lineage. Thus, direct cell–cell interactions through Efna.d play a critical role in patterning the ectoderm of the early ascidian embryo.     

Suspensor Length Determines Developmental Progression of the Embryo in Arabidopsis

The first structure that differentiates during plant embryogenesis is the extra-embryonic suspensor that positions the embryo in the lumen of the seed. A central role in nutrient transport has been ascribed to the suspensor in species with prominent suspensor structures. Little is known, however, about what impact the size of the rather simple Arabidopsis (Arabidopsis thaliana) suspensor has on embryogenesis. Here, we describe mutations in the predicted exo-polygalacturonase gene NIMNA (NMA) that lead to cell elongation defects in the early embryo and markedly reduced suspensor length. Mutant nma embryos develop slower than wild-type embryos, and we could observe a similar developmental delay in another mutant with shorter suspensors. Interestingly, for both genes, the paternal allele has a stronger influence on the embryonic phenotype. We conclude that the length of the suspensor is crucial for fast developmental progression of the embryo in Arabidopsis.Annual, self-pollinating weeds such as Arabidopsis (Arabidopsis thaliana) benefit from a short life cycle in their natural ephemeral habitats (Snell and Aarssen, 2005). A rapid progression through embryogenesis is a prerequisite for early seed maturation, and it is therefore not surprising that Arabidopsis sets up its body plan already after a very limited number of cell divisions (Aarssen, 2000; Lau et al., 2012).Arabidopsis embryogenesis starts with the fertilized egg cell, the zygote, which elongates about 3-fold before it divides asymmetrically. The smaller apical cell is the founder of the embryo proper that contributes to most of the later seedling, while the larger basal cell develops into a support structure called the suspensor (Jeong et al., 2011a). The suspensor is formed by a series of transverse cell divisions followed by longitudinal cell expansion forming a stalk-like structure. Only the upper-most suspensor cell, the hypophysis, will contribute to parts of the root meristem, while the rest of the suspensor remains extraembryonic and will cease its growth at the heart stage of the embryo (Yeung and Meinke, 1993). The suspensor is thought to be important for pushing the embryo into the lumen of the seed, where the embryo is surrounded by the nourishing endosperm. In addition, a key function in nutrient and hormone transport to the embryo is assigned to the suspensor (Kawashima and Goldberg, 2010).The Arabidopsis suspensor achieves its maximum length with a minimum number of cells by having a rod-shaped structure built by a single cell file. Although several mutants with distorted or shorter suspensors have been described in Arabidopsis, little is known about what impact suspensor length has on embryo development (Schwartz et al., 1994; Vernon and Meinke, 1994; Lukowitz et al., 2004; Breuninger et al., 2008; Bayer et al., 2009; Jeong et al., 2011b).As in all plant cells, the size and shape of suspensor cells is primarily determined by the elasticity of the cell wall. While rigid cellulose microfibrils determine the direction of cell expansion, it is the pectin matrix that plays a major role in determining the stiffness of the cell wall (Peaucelle et al., 2012). Several pectin-modifying enzymes have been described that modulate the elasticity of the cell wall. Among these, pectin methyl esterases that determine the degree of homogalacturonan methylation seem to be major players (Palin and Geitmann, 2012). Pectin-degrading enzymes such as polygalacturonases (PGs) have been implicated with cell expansion, but their role in this process is much less clear (Hadfield and Bennett, 1998).The pectin-rich middle lamella serves as cement to aid cell adhesion, and it is therefore not surprising that several PG genes are involved in dehiscence and abscission events (Rhee et al., 2003; González-Carranza et al., 2007, 2012; Ogawa et al., 2009). The expression profile of many PG genes correlates temporally and spatially with cell elongation and therefore implies a role in cell expansion (Sitrit et al., 1999). The exact function of PGs during cell elongation is still unclear, and the lack of elongation defects in loss-of-function mutants further complicates matters.Here, we describe mutations in a PG gene, which we called NIMNA (NMA), that severely affect cell elongation in the embryo and suspensor.We demonstrate that embryos with shorter suspensors show a significant delay in development during embryogenesis, possibly caused by reduced access to nutrients from the endosperm. Interestingly, reciprocal crosses reveal an unequal parental contribution to NMA function in cell elongation of the suspensor.     

Improving Maternal Care through a State-Wide Health Insurance Program: A Cost and Cost-Effectiveness Study in Rural Nigeria

Background

While the Nigerian government has made progress towards the Millennium Development Goals, further investments are needed to achieve the targets of post-2015 Sustainable Development Goals, including Universal Health Coverage. Economic evaluations of innovative interventions can help inform investment decisions in resource-constrained settings. We aim to assess the cost and cost-effectiveness of maternal care provided within the new Kwara State Health Insurance program (KSHI) in rural Nigeria.

Methods and Findings

We used a decision analytic model to simulate a cohort of pregnant women. The primary outcome is the incremental cost effectiveness ratio (ICER) of the KSHI scenario compared to the current standard of care. Intervention cost from a healthcare provider perspective included service delivery costs and above-service level costs; these were evaluated in a participating hospital and using financial records from the managing organisations, respectively. Standard of care costs from a provider perspective were derived from the literature using an ingredient approach. We generated 95% credibility intervals around the primary outcome through probabilistic sensitivity analysis (PSA) based on a Monte Carlo simulation. We conducted one-way sensitivity analyses across key model parameters and assessed the sensitivity of our results to the performance of the base case separately through a scenario analysis. Finally, we assessed the sustainability and feasibility of this program’s scale up within the State’s healthcare financing structure through a budget impact analysis. The KSHI scenario results in a health benefit to patients at a higher cost compared to the base case. The mean ICER (US$46.4/disability-adjusted life year averted) is considered very cost-effective compared to a willingness-to-pay threshold of one gross domestic product per capita (Nigeria, US$ 2012, 2,730). Our conclusion was robust to uncertainty in parameters estimates (PSA: median US$49.1, 95% credible interval 21.9–152.3), during one-way sensitivity analyses, and when cost, quality, cost and utilization parameters of the base case scenario were changed. The sustainability of this program’s scale up by the State is dependent on further investments in healthcare.

Conclusions

This study provides evidence that the investment made by the KSHI program in rural Nigeria is likely to have been cost-effective; however, further healthcare investments are needed for this program to be successfully expanded within Kwara State. Policy makers should consider supporting financial initiatives to reduce maternal mortality tackling both supply and demand issues in the access to care.     

Maternal Repression of the P Element Promoter in the Germline of Drosophila Melanogaster: A Model for the P Cytotype

The transposition of P elements in Drosophila melanogaster is regulated by products encoded by the P elements themselves. The P cytotype, which represses transposition and associated phenomena, exhibits both a maternal effect and maternal inheritance. The genetic and molecular mechanisms of this regulation are complex and not yet fully understood. In a previous study, using P-lacZ fusion genes, we have shown that P element regulatory products were able to inhibit the activity of the P promoter in somatic tissues. However, the repression observed did not exhibit the maternal effect characteristic of the P cytotype. With a similar approach, we have assayed in vivo the effect of P element regulatory products in the germline. We show that the P cytotype is able to repress the P promoter in the germline as well as in the soma. Furthermore, this repression exhibits a maternal effect restricted to the germline. On the basis of these new observations, we propose a model for the mechanism of P cytotype repression and its maternal inheritance.     

Zygotic Lethals with Specific Maternal Effect Phenotypes in Drosophila Melanogaster. I. Loci on the X Chromosome

In order to identify all X-linked zygotic lethal loci that exhibit a specific maternal effect on embryonic development, germline clonal analyses of X-linked zygotic lethal mutations have been performed. Two strategies were employed. In Screen A germline clonal analysis of 441 mutations at 211 previously mapped X-linked loci within defined regions was performed. In Screen B germline clonal analysis of 581 larval and pupal mutations distributed throughout the entire length of the X chromosome was performed. These approaches provide an 86% level of saturation for X-linked late zygotic lethals (larval and pupal) with specific maternal effect embryonic lethal phenotypes. The maternal effect phenotypes of these mutations are described.