Altered Fhod3 expression involved in progressive high-frequency hearing loss via dysregulation of actin polymerization stoichiometry in the cuticular plate
by Ely Cheikh Boussaty, Yuzuru Ninoyu, Leonardo R. Andrade, Qingzhong Li, Ryu Takeya, Hideki Sumimoto, Takahiro Ohyama, Karl J. Wahlin, Uri Manor, Rick A. Friedman Age-related hearing loss (ARHL) is a common sensory impairment with complex underlying mechanisms. In our previous study, we performed a meta-analysis of genome-wide association studies (GWAS) in mice and identified a novel locus on chromosome 18 associated with ARHL specifically linked to a 32 kHz tone burst stimulus. Consequently, we investigated the role of Formin Homology 2 Domain Containing 3 (Fhod3), a newly discovered candidate gene for ARHL based on the...
Source: PLoS Genetics - March 18, 2024 Category: Genetics & Stem Cells Authors: Ely Cheikh Boussaty Source Type: research

Uncharted territories: Solving the mysteries of male meiosis in flies
by LingSze Lee, Leah F. Rosin The segregation of homologous chromosomes during meiosis typically requires tight end-to-end chromosome pairing. However, inDrosophila spermatogenesis, male flies segregate their chromosomes without classic synaptonemal complex formation and without recombination, instead compartmentalizing homologs into subnuclear domains known as chromosome territories (CTs). How homologs find each other in the nucleus and are separated into CTs has been one of the biggest riddles in chromosome biology. Here, we discuss our current understanding of pairing and CT formation in flies and review recent data on...
Source: PLoS Genetics - March 15, 2024 Category: Genetics & Stem Cells Authors: LingSze Lee Source Type: research

P53 and BCL-2 family proteins PUMA and NOXA define competitive fitness in pluripotent cell competition
by Jose A. Valverde-Lopez, Lin Li-Bao, Roc ío Sierra, Elisa Santos, Giovanna Giovinazzo, Covadonga Díaz-Díaz, Miguel Torres Cell Competition is a process by which neighboring cells compare their fitness. As a result, viable but suboptimal cells are selectively eliminated in the presence of fitter cells. In the early mammalian embryo, epiblast pluripotent cells undergo extensive Cell Competition, which prevents suboptimal cells from contributing to the newly forming organism. While competitive ability is regulated by MYC in the epiblast, the mechanisms that contribute to competitive fitness in this context are largely u...
Source: PLoS Genetics - March 15, 2024 Category: Genetics & Stem Cells Authors: Jose A. Valverde-Lopez Source Type: research

A fatty acid anabolic pathway in specialized-cells sustains a remote signal that controls egg activation in < i > Drosophila < /i >
by Mickael Poidevin, Nicolas Mazuras, Gw énaëlle Bontonou, Pierre Delamotte, Béatrice Denis, Maëlle Devilliers, Perla Akiki, Delphine Petit, Laura de Luca, Priscilla Soulie, Cynthia Gillet, Claude Wicker-Thomas, Jacques Montagne Egg activation, representing the critical oocyte-to-embryo transition, provokes meiosis completion, modification of the vitelline membrane to prevent polyspermy, and translation of maternally provided mRNAs. This transition is triggered by a calcium signal induced by spermatozoon fertilization in most animal species, but not in insects. InDrosophila melanogaster, mature oocytes remain arrested...
Source: PLoS Genetics - March 14, 2024 Category: Genetics & Stem Cells Authors: Mickael Poidevin Source Type: research

INSIDER: Interpretable sparse matrix decomposition for RNA expression data analysis
by Kai Zhao, Sen Huang, Cuichan Lin, Pak Chung Sham, Hon-Cheong So, Zhixiang Lin RNA sequencing (RNA-Seq) is widely used to capture transcriptome dynamics across tissues, biological entities, and conditions. Currently, few or no methods can handle multiple biological variables (e.g., tissues/ phenotypes) and their interactions simultaneously, while also achieving dimension reduction (DR). We propose INSIDER, a general and flexible statistical framework based on matrix factorization, which is freely available at https://github.com/kai0511/insider. INSIDER decomposes variation from different biological variables and their i...
Source: PLoS Genetics - March 14, 2024 Category: Genetics & Stem Cells Authors: Kai Zhao Source Type: research

Functional labeling of individualized postsynaptic neurons using optogenetics and < i > trans- < /i > Tango in < i > Drosophila < /i > (FLIPSOT)
In this study, we developed FLIPSOT, or functional labeling of individualized postsynaptic neurons using optogenetics andtrans-Tango. FLIPSOT uses (1)trans-Tango to access postsynaptic neurons genetically, (2) optogenetic approaches to activate (FLIPSOTa) or inhibit (FLIPSOTi) postsynaptic neurons in a random and sparse manner, and (3) fluorescence markers tagged with optogenetic genes to visualize these neurons. Therefore, FLIPSOT allows using a presynaptic driver to identify the behavioral function of individual postsynaptic neurons. It is readily applied to identify functions of individual postsynaptic neurons and has t...
Source: PLoS Genetics - March 14, 2024 Category: Genetics & Stem Cells Authors: Allison N. Castaneda Source Type: research

Transposition of < i > HOPPLA < /i > in siRNA-deficient plants suggests a limited effect of the environment on retrotransposon mobility in < i > Brachypodium distachyon < /i >
by Michael Thieme, Nikolaos Minadakis, Christophe Himber, Bettina Keller, Wenbo Xu, Kinga Rutowicz, Calvin Matteoli, Marcel B öhrer, Bart Rymen, Debbie Laudencia-Chingcuanco, John Vogel, Richard Sibout, Christoph Stritt, Todd Blevins, Anne C. Roulin Long terminal repeat retrotransposons (LTR-RTs) are powerful mutagens regarded as a major source of genetic novelty and important drivers of evolution. Yet, the uncontrolled and potentially selfish proliferation of LTR-RTs can lead to deleterious mutations and genome instability, with large fitness costs for their host. While population genomics data suggest that an ongoing L...
Source: PLoS Genetics - March 12, 2024 Category: Genetics & Stem Cells Authors: Michael Thieme Source Type: research

A negative feedback loop is critical for recovery of RpoS after stress in < i > Escherichia coli < /i >
by Sophie Bouillet, Issam Hamdallah, Nadim Majdalani, Arti Tripathi, Susan Gottesman RpoS is an alternative sigma factor needed for the induction of the general stress response in many gammaproteobacteria. Tight regulation of RpoS levels and activity is required for bacterial growth and survival under stress. InEscherichia coli, various stresses lead to higher levels of RpoS due to increased translation and decreased degradation. During non-stress conditions, RpoS is unstable, because the adaptor protein RssB delivers RpoS to the ClpXP protease. RpoS degradation is prevented during stress by the sequestration of RssB by a...
Source: PLoS Genetics - March 11, 2024 Category: Genetics & Stem Cells Authors: Sophie Bouillet Source Type: research

A single amino acid polymorphism in natural Metchnikowin alleles of < i > Drosophila < /i > results in systemic immunity and life history tradeoffs
by Jessamyn I. Perlmutter, Joanne R. Chapman, Mason C. Wilkinson, Isaac Nevarez-Saenz, Robert L. Unckless Antimicrobial peptides (AMPs) are at the interface of interactions between hosts and microbes and are therefore expected to be rapidly evolving in a coevolutionary arms race with pathogens. In contrast, previous work demonstrated that insect AMPs tend to evolve more slowly than the genome average. Metchikowin (Mtk) is aDrosophila AMP that has a single amino acid residue that segregates as either proline (P) or arginine (R) in populations of four different species, some of which diverged more than 10 million years ago....
Source: PLoS Genetics - March 11, 2024 Category: Genetics & Stem Cells Authors: Jessamyn I. Perlmutter Source Type: research

Ecdysone-controlled nuclear receptor ERR regulates metabolic homeostasis in the disease vector mosquito < i > Aedes aegypti < /i >
In this study, we found that the expression of estrogen-related receptor (ERR), a nuclear receptor, is activated by the direct binding of 20-hydroxyecdysone (20E) and ecdysone receptor (EcR) to the ecdysone response element (EcRE) in theERR promoter region during the gonadotropic cycle ofAedes aegypti (named AaERR). RNA interference (RNAi) ofAaERR in female mosquitoes led to delayed development of ovaries. mRNA abundance of genes encoding key enzymes involved in carbohydrate metabolism (CM) —glucose-6-phosphate isomerase (GPI) andpyruvate kinase (PYK) —was significantly decreased inAaERR knockdown mosquitoes, while the...
Source: PLoS Genetics - March 11, 2024 Category: Genetics & Stem Cells Authors: Dan-Qian Geng Source Type: research

The regulation of methylation on the Z chromosome and the identification of multiple novel Male Hyper-Methylated regions in the chicken
by Andrey H öglund, Rie Henriksen, Allison M. Churcher, Carlos M. Guerrero-Bosagna, Alvaro Martinez-Barrio, Martin Johnsson, Per Jensen, Dominic Wright DNA methylation is a key regulator of eukaryote genomes, and is of particular relevance in the regulation of gene expression on the sex chromosomes, with a key role in dosage compensation in mammalian XY systems. In the case of birds, dosage compensation is largely absent, with it being restricted to two small Male Hyper-Methylated (MHM) regions on the Z chromosome. To investigate how variation in DNA methylation is regulated on the Z chromosome we utilised a wild x domes...
Source: PLoS Genetics - March 8, 2024 Category: Genetics & Stem Cells Authors: Andrey H öglund Source Type: research

Succinate utilisation by < i > Salmonella < /i > is inhibited by multiple regulatory systems
by Nicolas Wenner, Xiaojun Zhu, Will P. M. Rowe, Kristian H ändler, Jay C. D. Hinton Succinate is a potent immune signalling molecule that is present in the mammalian gut and within macrophages. Both of these infection niches are colonised by the pathogenic bacteriumSalmonella enterica serovar Typhimurium during infection. Succinate is a C4-dicarboyxlate that can serve as a source of carbon for bacteria. When succinate is provided as the sole carbon source forin vitro cultivation,Salmonella and other enteric bacteria exhibit a slow growth rate and a long lag phase. This growth inhibition phenomenon was known to involve t...
Source: PLoS Genetics - March 8, 2024 Category: Genetics & Stem Cells Authors: Nicolas Wenner Source Type: research

Long-read sequencing for fast and robust identification of correct genome-edited alleles: PCR-based and Cas9 capture methods
ConclusionTargeted long-read sequencing supports in-depth characterisation of all experimental models that aim to produce knock-in or conditional alleles, including those that contain a mix of genome-edited alleles. PCR- or Cas9 capture-based modalities bring different advantages to the analysis. (Source: PLoS Genetics)
Source: PLoS Genetics - March 8, 2024 Category: Genetics & Stem Cells Authors: Christopher V. McCabe Source Type: research

New insights into the all-testis differentiation in zebrafish with compromised endogenous androgen and estrogen synthesis
by Yonglin Ruan, Xuehui Li, Xinyi Wang, Gang Zhai, Qiyong Lou, Xia Jin, Jiangyan He, Jie Mei, Wuhan Xiao, Jianfang Gui, Zhan Yin The regulatory mechanism of gonadal sex differentiation, which is complex and regulated by multiple factors, remains poorly understood in teleosts. Recently, we have shown that compromised androgen and estrogen synthesis with increased progestin leads to all-male differentiation with proper testis development and spermatogenesis incytochrome P450 17a1 (cyp17a1)-/- zebrafish. In the present study, the phenotypes of female-biased sex ratio were positively correlated with higherFanconi anemia compl...
Source: PLoS Genetics - March 7, 2024 Category: Genetics & Stem Cells Authors: Yonglin Ruan Source Type: research

The PP2A-like phosphatase Ppg1 mediates assembly of the Far complex to balance gluconeogenic outputs and enables adaptation to glucose depletion
by Shreyas Niphadkar, Lavanya Karinje, Sunil Laxman To sustain growth in changing nutrient conditions, cells reorganize outputs of metabolic networks and appropriately reallocate resources. Signaling by reversible protein phosphorylation can control such metabolic adaptations. In contrast to kinases, the functions of phosphatases that enable metabolic adaptation as glucose depletes are poorly studied. Using aSaccharomyces cerevisiae deletion screen, we identified the PP2A-like phosphatase Ppg1 as required for appropriate carbon allocations towards gluconeogenic outputs —trehalose, glycogen, UDP-glucose, UDP-GlcNAc—aft...
Source: PLoS Genetics - March 7, 2024 Category: Genetics & Stem Cells Authors: Shreyas Niphadkar Source Type: research