The LARGE2-APO1/APO2 regulatory module controls panicle size and grain number in rice

2021 ◽  
Author(s):  
Luojiang Huang ◽  
Kai Hua ◽  
Ran Xu ◽  
Dali Zeng ◽  
Ruci Wang ◽  
...  
Keyword(s):  
Agronomic Traits ◽  
Loss Of Function ◽  
Grain Number ◽  
Hect Domain ◽  
Regulatory Module ◽  
Promising Target ◽  
Meristematic Activity ◽  
Positive Regulators ◽  
Genetic Mechanisms ◽  
Biochemical Analyses

Abstract Panicle size and grain number are important agronomic traits and influence grain yield in rice (Oryza sativa), but the molecular and genetic mechanisms underlying panicle size and grain number control remain largely unknown in crops. Here we report that LARGE2 encodes a HECT-domain E3 ubiquitin ligase OsUPL2 and regulates panicle size and grain number in rice. The loss of function large2 mutants produce large panicles with increased grain number, wide grains and leaves, and thick culms. LARGE2 regulates panicle size and grain number by repressing meristematic activity. LARGE2 is highly expressed in young panicles and grains. Biochemical analyses show that LARGE2 physically associates with ABERRANT PANICLE ORGANIZATION1 (APO1) and APO2, two positive regulators of panicle size and grain number, and modulates their stabilities. Genetic analyses support that LARGE2 functions with APO1 and APO2 in a common pathway to regulate panicle size and grain number. These findings reveal a novel genetic and molecular mechanism of the LARGE2-APO1/APO2 module-mediated control of panicle size and grain number in rice, suggesting that this module is a promising target for improving panicle size and grain number in crops.

Genetic control of dorsal-ventral identity in the telencephalon: opposing roles for Pax6 and Gsh2

Development ◽  
2000 ◽  
Vol 127 (20) ◽  
pp. 4361-4371 ◽  
Author(s):  
H. Toresson ◽  
S.S. Potter ◽  
K. Campbell
Keyword(s):  
Cerebral Cortex ◽  
Gene Function ◽  
Abnormal Development ◽  
Loss Of Function ◽  
Embryonic Mouse ◽  
Molecular Identity ◽  
Mouse Mutants ◽  
Germinal Zone ◽  
Genetic Mechanisms ◽  
Dlx Genes

We have examined the genetic mechanisms that regulate dorsal-ventral identity in the embryonic mouse telencephalon and, in particular, the specification of progenitors in the cerebral cortex and striatum. The respective roles of Pax6 and Gsh2 in cortical and striatal development were studied in single and double loss-of-function mouse mutants. Gsh2 gene function was found to be essential to maintain the molecular identity of early striatal progenitors and in its absence the ventral telencephalic regulatory genes Mash1 and Dlx are lost from most of the striatal germinal zone. In their place, the dorsal regulators, Pax6, neurogenin 1 and neurogenin 2 are found ectopically. Conversely, Pax6 is required to maintain the correct molecular identity of cortical progenitors. In its absence, neurogenins are lost from the cortical germinal zone and Gsh2, Mash1 and Dlx genes are found ectopically. These reciprocal alterations in cortical and striatal progenitor specification lead to the abnormal development of the cortex and striatum observed in Pax6 (small eye) and Gsh2 mutants, respectively. In support of this, double homozygous mutants for Pax6 and Gsh2 exhibit significant improvements in both cortical and striatal development compared with their respective single mutants. Taken together, these results demonstrate that Pax6 and Gsh2 govern cortical and striatal development by regulating genetically opposing programs that control the expression of each other as well as the regionally expressed developmental regulators Mash1, the neurogenins and Dlx genes in telencephalic progenitors.

scholarly journals Canaryseed (Phalaris canariensis L.) accessions from nineteen countries show useful genetic variation for agronomic traits

2011 ◽  
Vol 91 (1) ◽  
pp. 37-48 ◽  
Author(s):  
M. Cogliatti ◽  
F. Bongiorno ◽  
H. Dalla Valle ◽  
W J Rogers
Keyword(s):  
Genetic Variation ◽  
Grain Yield ◽  
Harvest Index ◽  
Agronomic Traits ◽  
Grain Weight ◽  
Environment Interaction ◽  
Grain Number ◽  
Harvest Maturity ◽  
Phalaris Canariensis ◽  
Late Sowing

Fifty-seven accessions of canaryseed (47 populations and 10 cultivars) from 19 countries were evaluated for agronomic traits in four field trials sown over 3 yr in the province of Buenos Aires, Argentina. Genetic variation was found for all traits scored: grain yield and its components (grain weight, grain number per square meter, grain number per head and head number per square meter), harvest index, percent lodging, and phenological characters (emergence to heading, emergence to harvest maturity and heading to harvest maturity). Although genotype × environment interaction was observed for all traits, the additive differences between accessions were sufficient to enable promising breeding materials to be identified. Accessions superior in performance to the local Argentinean population, which in general gave values close to the overall mean of the accessions evaluated, were identified. For example, a population of Moroccan origin gave good yield associated with elevated values of the highly heritable character grain weight, rather than with the more commonly observed grain number per square meter. This population was also of relatively short stature and resistant to lodging, and, although it performed best when sown within the normal sowing date, tolerated late sowing fairly well. Other accessions were also observed with high grain weight, a useful characteristic in itself, since large grains are desirable from a quality point of view. Regarding phenology, the accessions showed a range of 160 degree days (8 calendar days in our conditions) in maturity, which, while not large in magnitude, may be of some utility in crop rotation management. Some accessions were well adapted to late sowing. Grain yield in general was strongly correlated with grain number per square meter. Principal components analysis (PCA) carried out for all characteristics provided indications of accessions combining useful characteristics and identified three components that explained approximately 70% of the phenotypic variation. Furthermore, a second PCA plus regression showed that approximately 60% of the variation in grain yield could be explained by a component associated with harvest index and grain number per square meter. Pointers were provided to possible future breeding targets.Key words: Phalaris canariensis, canaryseed, accessions, yield, phenology, genetics, breeding

scholarly journals Hypolipidemia associated with inactivation of TM6SF2 is due to decreased VLDL-lipids secretion

2021 ◽  
Vol 42 (Supplement_1) ◽  
Author(s):  
F Luo ◽  
E Smagris ◽  
J A Fletcher ◽  
J C Cohen ◽  
H H Hobbs
Keyword(s):  
Plasma Lipid ◽  
Microscopic Analysis ◽  
Missense Variant ◽  
Cell Fractionation ◽  
Loss Of Function ◽  
Lipid Levels ◽  
Funding Sources ◽  
Golgi Compartment ◽  
Exon 1 ◽  
Biochemical Analyses

Abstract Background A missense variant in Transmembrane 6 Superfamily Member 2 [TM6SF2 (E167K)] is associated with reduced plasma lipid levels and protection from coronary atherosclerosis. The substitution of lysine for glutamate at residue 167 is associated with a marked decrease in TM6SF2 protein expression, consistent with a loss-of-function mutation. However the biological role of TM6SF2 is not known, and the mechanism(s) responsible for the hypolipidemia associated with mutation gene has not been fully defined. To elucidate the pathological mechanism for the hypolipidemia associated with TM6SF2 deficiency, we inactivated Tm6sf2 in mice and rats. Methods Tm6sf2−/− mice were generated as described previously. Two lines of Tm6sf2−/− rats with different frameshift mutations in exon 1 were generated using CRISPR/Cas9 technology. Primary hepatocytes were isolated from WT and Tm6sf2−/− mice for microscopy. Rats were fasted 16 or 4 hours and tissues were collected on ice for cell fractionation, and in liquid nitrogen for biochemical analyses. Frozen samples were stored at −80°C for subsequent analyses. Result In both mice and rats, inactivation of Tm6sf2 recapitulated the phenotype of humans with the E167K substitution: steatosis, reduced plasma lipid levels, and transaminitis. The phenotype was readily apparent in animals fed chow diets. Both species had reduced secretion of VLDL-TG, as determined by TRITON WR1399 injection, with no decrease in secretion of ApoB. Experiments in isolated perfused livers from WT and Tm6sf2−/− mice confirmed that the decreased TG secretion observed in intact animals reflected reduced TG secretion from the liver. Lipidomic analysis of the liver perfusates by by LC-MS indicated that secretion of cholesteryl esters, and phospholipids was also decreased in the KO animals. Taken together, these findings are consistent with a role for TM6SF2 in lipidation of ApoB-containing lipoproteins. To further elucidate the function of TM6SF2, we used fluorescence microscopy and cell fractionation to determine the subcellular localization of the protein. Microscopic analysis showed that TM6SF2 co-localized with ER and Golgi markers, but cell fractionation studies indicated that the protein is located primarily in the smooth ER. The ratio of TG to ApoB was lower in Golgi fractions from TM6sf2−/− rats than in corresponding fractions from WT animals. Conclusions Since the sequela of TM6SF2 inactivation are already apparent in the Golgi, we speculate that TM6SF2 promotes lipidation of VLDL in a pre-Golgi compartment. We are currently performing additional studies to further define the specific mechanism whereby TM6SF2 promotes lipidation of ApoB-containing lipoproteins. FUNDunding Acknowledgement Type of funding sources: Foundation. Main funding source(s): National Institutes of Health

scholarly journals Fertility of Pedicellate Spikelets in Sorghum is Controlled by a Jasmonic Acid Regulatory Module

2019 ◽  
Author(s):  
Nicholas Gladman ◽  
Yinping Jiao ◽  
Young Koung Lee ◽  
Lifang Zhang ◽  
Ratan Chopra ◽  
...  
Keyword(s):  
Transcription Factor ◽  
Jasmonic Acid ◽  
Sorghum Bicolor ◽  
Spikelet Fertility ◽  
Cereal Crops ◽  
Grain Number ◽  
Regulatory Module ◽  
Induced Module ◽  
Acid Pathway ◽  
Floral Meristems

AbstractAs in other cereal crops, the panicles of sorghum (Sorghum bicolor (L.) Moench) comprise two types of floral spikelets (grass flowers). Only sessile spikelets (SSs) are capable of producing viable grains, whereas pedicellate spikelets (PSs) cease development after initiation and eventually abort. Consequently, grain number per panicle (GNP) is lower than the total number of flowers produced per panicle. The mechanism underlying this differential fertility is not well understood. To investigate this issue, we isolated a series of EMS-induced multiseeded (msd) mutants that result in full spikelet fertility, effectively doubling GNP. Previously, we showed that MSD1 is a TCP (Teosinte branched/Cycloidea/PCF) transcription factor that regulates jasmonic acid (JA) biosynthesis, and ultimately floral sex organ development. Here, we show that MSD2 encodes a lipoxygenase (LOX) that catalyzes the first committed step of JA biosynthesis. Further, we demonstrate that MSD1 binds to the promoters of MSD2 and other JA pathway genes. Together, these results show that a JA-induced module regulates sorghum panicle development and spikelet fertility. The findings advance our understanding of inflorescence development and could lead to new strategies for increasing GNP and grain yield in sorghum and other cereal crops.SignificanceThrough a single base pair mutation, grain number can be increased by ~200% in the globally important crop Sorghum bicolor. This mutation affects the expression of an enzyme, MSD2, that catalyzes the jasmonic acid pathway in developing floral meristems. The global gene expression profile in this enzymatic mutant is similar to that of a transcription factor mutant, msd1, indicating that disturbing any component of this regulatory module disrupts a positive feedback loop that occurs normally due to regular developmental perception of jasmonic acid. Additionally, the MSD1 transcription factor is able to regulate MSD2 in addition to other jasmonic acid pathway genes, suggesting that it is a primary transcriptional regulator of this hormone signaling pathway in floral meristems.

scholarly journals ARID1A Regulates Transcription and the Epigenetic Landscape via POLE and DMAP1 While ARID1A Deficiency or Pharmacological Inhibition Sensitizes Germ Cell Tumor Cells to ATR Inhibition

Cancers ◽  
2020 ◽  
Vol 12 (4) ◽  
pp. 905 ◽  
Author(s):  
Lukas Kurz ◽  
Alissa Miklyaeva ◽  
Margaretha A. Skowron ◽  
Nina Overbeck ◽  
Gereon Poschmann ◽  
...  
Keyword(s):  
Germ Cell ◽  
Dna Methyltransferase ◽  
Synthetic Lethality ◽  
Germ Cell Tumors ◽  
Epigenetic Landscape ◽  
Loss Of Function ◽  
Pharmacological Inhibition ◽  
Promising Target ◽  
Cure Rates ◽  
Tumor Types

Germ cell tumors (GCTs) are the most common solid malignancies found in young men. Although they generally have high cure rates, metastases, resistance to cisplatin-based therapy, and late toxicities still represent a lethal threat, arguing for the need of new therapeutic options. In a previous study, we identified downregulation of the chromatin-remodeling SWI/SNF complex member ARID1A as a key event in the mode of action of the histone deacetylase inhibitor romidepsin. Additionally, the loss-of-function mutations re-sensitize different tumor types to various drugs, like EZH2-, PARP-, HDAC-, HSP90- or ATR-inhibitors. Thus, ARID1A presents as a promising target for synthetic lethality and combination therapy. In this study, we deciphered the molecular function of ARID1A and screened for the potential of two pharmacological ARID1A inhibitors as a new therapeutic strategy to treat GCTs. By CRISPR/Cas9, we generated ARID1A-deficient GCT cells and demonstrate by mass spectrometry that ARID1A is putatively involved in regulating transcription, DNA repair and the epigenetic landscape via DNA Polymerase POLE and the DNA methyltransferase 1-associated protein DMAP1. Additionally, ARID1A/ARID1A deficiency or pharmacological inhibition increased the efficacy of romidepsin and considerably sensitized GCT cells, including cisplatin-resistant subclones, towards ATR inhibition. Thus, targeting ARID1A in combination with romidepsin and ATR inhibitors presents as a new putative option to treat GCTs.

scholarly journals Apoptosis Modulation as a Promising Target for Treatment of Systemic Sclerosis

2011 ◽  
Vol 2011 ◽  
pp. 1-13 ◽  
Author(s):  
Stéphane Chabaud ◽  
Véronique J. Moulin
Keyword(s):  
Systemic Sclerosis ◽  
Autoimmune Disease ◽  
Therapeutic Targets ◽  
Immune Dysfunction ◽  
Vascular Damage ◽  
Loss Of Function ◽  
Internal Organs ◽  
Promising Target ◽  
New Findings ◽  
Diffuse Systemic Sclerosis

Diffuse systemic sclerosis (SSc) is a fatal autoimmune disease characterized by an excessive ECM deposition inducing a loss of function of skin and internal organs. Apoptosis is a key mechanism involved in all the stages of the disease: vascular damage, immune dysfunction, and fibrosis. The purpose of this paper is to gather new findings in apoptosis related to SSc, to highlight relations between apoptosis and fibrosis, and to identify new therapeutic targets.

scholarly journals ALKALs are in vivo ligands for ALK family receptor tyrosine kinases in the neural crest and derived cells

2018 ◽  
Vol 115 (4) ◽  
pp. E630-E638 ◽  
Author(s):  
Andrey Fadeev ◽  
Patricia Mendoza-Garcia ◽  
Uwe Irion ◽  
Jikui Guan ◽  
Kathrin Pfeifer ◽  
...  
Keyword(s):  
Neural Crest ◽  
Tyrosine Kinases ◽  
Pigment Cells ◽  
Loss Of Function ◽  
Pediatric Tumor ◽  
Downstream Signaling ◽  
Receptor Complexes ◽  
Anaplastic Lymphoma ◽  
Biochemical Analyses

Mutations in anaplastic lymphoma kinase (ALK) are implicated in somatic and familial neuroblastoma, a pediatric tumor of neural crest-derived tissues. Recently, biochemical analyses have identified secreted small ALKAL proteins (FAM150, AUG) as potential ligands for human ALK and the related leukocyte tyrosine kinase (LTK). In the zebrafish Danio rerio, DrLtk, which is similar to human ALK in sequence and domain structure, controls the development of iridophores, neural crest-derived pigment cells. Hence, the zebrafish system allows studying Alk/Ltk and Alkals involvement in neural crest regulation in vivo. Using zebrafish pigment pattern formation, Drosophila eye patterning, and cell culture-based assays, we show that zebrafish Alkals potently activate zebrafish Ltk and human ALK driving downstream signaling events. Overexpression of the three DrAlkals cause ectopic iridophore development, whereas loss-of-function alleles lead to spatially distinct patterns of iridophore loss in zebrafish larvae and adults. alkal loss-of-function triple mutants completely lack iridophores and are larval lethal as is the case for ltk null mutants. Our results provide in vivo evidence of (i) activation of ALK/LTK family receptors by ALKALs and (ii) an involvement of these ligand–receptor complexes in neural crest development.

scholarly journals  Influence of crop management upon the agronomic traits of spelt (Triticum spelta L.)    

2011 ◽  
Vol 57 (No. 9) ◽  
pp. 435-440 ◽  
Author(s):  
S. Pospisil A Pospisil M Svecnjak Z Matotan
Keyword(s):  
Grain Yield ◽  
Yield Components ◽  
Agronomic Traits ◽  
Seeding Rate ◽  
Grain Number ◽  
Triticum Spelta ◽  
Fungicide Treatment ◽  
Growing Seasons ◽  
1000 Grain Weight ◽  
Germinated Seeds

  Investigations were carried out at the experimental field of the Faculty of Agriculture in Zagreb in the growing seasons 2008/2009 and 2009/2010 with the aim to determine the influence of seeding rate and fungicide treatment upon the yield and yield components of spelt (Triticum spelta L.). The trial included two spelt cultivars: Nirvana and Ostro, three seeding rates: 200, 300, and 400 germinated seeds/m2, and a fungicide treatment (tebuconazole). Cultivar Nirvana produced a significantly higher grain yield in both trial years, higher number of spikelets per spike, higher grain number and mass per spike. Cultivar Ostro had a significantly higher grain crude proteins content, higher 1000 grain weight, and also a higher number of sterile spikelets per spike. No significant effect of seeding rate on grain yield was determined while the fungicide treatment had a significant effect on grain yield only in the warmer year 2008/2009.

scholarly journals Artificial Selection for Pathogenicity Mutations inStaphylococcus aureusIdentifies Novel Factors Relevant to Chronic Infection

2019 ◽  
Vol 87 (4) ◽  
Author(s):  
Kathryn McLean ◽  
Elizabeth A. Holmes ◽  
Kelsi Penewit ◽  
Duankun K. Lee ◽  
Samantha R. Hardy ◽  
...  
Keyword(s):  
Artificial Selection ◽  
Chronic Infection ◽  
Loss Of Function ◽  
Diverse Range ◽  
Content Type ◽  
Transposon Mutants ◽  
Genetic Mechanisms ◽  
Functionally Diverse ◽  
Chromosomal Mutations ◽  
Virulence Regulator

ABSTRACTAdaptation ofStaphylococcus aureusto host microenvironments during chronic infection involves spontaneous mutations, yet changes underlying adaptive phenotypes remain incompletely explored. Here, we employed artificial selection and whole-genome sequencing to better characterize spontaneous chromosomal mutations that alter two pathogenicity phenotypes relevant to chronic infection inS. aureus: intracellular invasiveness and intracellular cytotoxicity. We identified 23 genes whose alteration coincided with enhanced virulence, 11 that were previously known and 12 (52%) that had no previously described role inS. aureuspathogenicity. Using precision genome editing, transposon mutants, and gene complementation, we empirically assessed the contributions of individual genes to the two virulence phenotypes. We functionally validated 14 of 21 genes tested as measurably influencing invasion and/or cytotoxicity, including 8 newly implicated by this study. We identified inactivating mutations (murA,ndhC, and a hypothetical membrane protein) and gain-of-function mutations (aroEThr182Ile,yhcFThr74Ile, and Asp486Glu in a hypothetical peptidase) in previously unrecognizedS. aureusvirulence genes that enhance pathogenesis when introduced into a clean genetic background, as well as a novel activating mutation in the known virulence regulator genesaeS(Ala106Thr). Investigation of potentially epistatic interactions identified atufAmutation (Ala271Val) that enhances virulence only in the context of purine operon repressor gene (purR) inactivation. This project reveals a functionally diverse range of genes affected by gain- or loss-of-function mutations that contribute toS. aureusadaptive virulence phenotypes. More generally, the work establishes artificial selection as a means to determine the genetic mechanisms underlying complex bacterial phenotypes relevant to adaptation during infection.

scholarly journals Genetic Diversity of Genetic Resources of Winter Barley Maintained in the Genebank in Slovakia

2011 ◽  
Vol 40 (No. 4) ◽  
pp. 118-126 ◽  
Author(s):  
M. Žáková ◽  
M. Benková
Keyword(s):  
Genetic Resources ◽  
Agronomic Traits ◽  
Vegetation Period ◽  
Winter Barley ◽  
Multivariate Methods ◽  
Agronomic Characters ◽  
Grain Number ◽  
High Positive Correlation ◽  
Selected Traits ◽  
Full Maturity

A set of 140 winter barley genetic resources of foreign and domestic origins was tested on experimental basis of RIPP in 1997–1999 to characterise the variability of the accessions based on agronomic data using multivariate methods. In the set tested, variability was studied of selected traits and characteristics such as: plant height (PH), weight of 1000 grains (W), grain number per a spike (SNG), grain uniformity – ratio of front seeds over 2.5  m sieve (GU), vegetation period – sowing/full maturity (VM) and seed yield (Y). Agronomic characters show great variability between cultivars. The study of matrix interrelationships between different variables showed that the yield is greatly correlated with traits:  vegetation period – sowing/full maturity, grain uniformity and grain number per a spike. High positive correlation was obtained between the grain uniformity and the weight of 1000 grains. Negative correlation was found between the grain number per a spike and weight of 1000 grains in six-row barley. Correlations between agronomic traits differed between two- and six-row barley sets. The study revealed the existence of genetic differences among accessions as well as differences between two- and six-row winter barley and between the genotypes of domestic and foreign country origin, respectively. Results of this study provided information about diversity which should be of particular interest for the further collecting of genetic resources.  

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