scholarly journals De Novo Phosphoinositide Synthesis in Zebrafish Is Required for Triad Formation but Not Essential for Myogenesis

2020 ◽  
Author(s):  
Lindsay Smith ◽  
Lacramioara Fabian ◽  
Almundher Al-Maawali ◽  
Ramil R. Noche ◽  
James J. Dowling
Keyword(s):  
Muscle Development ◽  
De Novo ◽  
Structural Defects ◽  
Vertebrate Development ◽  
Cellular Processes ◽  
Regulatory Enzymes ◽  
Muscle Formation ◽  
Theory Result ◽  
The Impact

AbstractPhosphoinositides (PIPs) and their regulatory enzymes are key players in many cellular processes and are required for aspects of vertebrate development. Dysregulated PIP metabolism has been implicated in several human diseases, including a subset of skeletal myopathies that feature structural defects in the triad. The role of PIPs in skeletal muscle formation, and particularly triad biogenesis, has yet to be determined. CDP-diacylglycerol-inositol 3-phosphatidyltransferase (CDIPT) catalyzes the formation of phosphatidylinositol, which is the base of all PIP species. Loss of CDIPT should, in theory, result in the failure to produce PIPs, and thus provide a strategy for establishing the requirement for PIPs during embryogenesis. In this study, we generated cdipt mutant zebrafish and determined the impact on skeletal myogenesis. Analysis of cdipt mutant muscle revealed no apparent global effect on early muscle development. However, small but significant defects were observed in triad size, with T-tubule area, inter terminal cisternae distance and gap width being smaller in cdipt mutants. This was associated with a decrease in motor performance. Overall, these data suggest that myogenesis in zebrafish does not require de novo PIP synthesis but does implicate a role for CDIPT in triad formation.

scholarly journals Interphotoreceptor coupling: an evolutionary perspective

2021 ◽  
Author(s):  
Lorenzo Cangiano ◽  
Sabrina Asteriti
Keyword(s):  
Visual Information ◽  
Signal To Noise Ratio ◽  
Electrical Coupling ◽  
Physiological Role ◽  
Cellular Processes ◽  
Contact Points ◽  
Highly Sensitive ◽  
The Many ◽  
The Impact

AbstractIn the vertebrate retina, signals generated by cones of different spectral preference and by highly sensitive rod photoreceptors interact at various levels to extract salient visual information. The first opportunity for such interaction is offered by electrical coupling of the photoreceptors themselves, which is mediated by gap junctions located at the contact points of specialised cellular processes: synaptic terminals, telodendria and radial fins. Here, we examine the evolutionary pressures for and against interphotoreceptor coupling, which are likely to have shaped how coupling is deployed in different species. The impact of coupling on signal to noise ratio, spatial acuity, contrast sensitivity, absolute and increment threshold, retinal signal flow and colour discrimination is discussed while emphasising available data from a variety of vertebrate models spanning from lampreys to primates. We highlight the many gaps in our knowledge, persisting discrepancies in the literature, as well as some major unanswered questions on the actual extent and physiological role of cone-cone, rod-cone and rod-rod communication. Lastly, we point toward limited but intriguing evidence suggestive of the ancestral form of coupling among ciliary photoreceptors.

scholarly journals Contribution of retrotransposition to developmental disorders

2019 ◽  
Vol 10 (1) ◽  
Author(s):  
Eugene J. Gardner ◽  
Elena Prigmore ◽  
Giuseppe Gallone ◽  
Petr Danecek ◽  
Kaitlin E. Samocha ◽  
...  
Keyword(s):  
Developmental Disorders ◽  
De Novo ◽  
Purifying Selection ◽  
Selective Constraint ◽  
Protein Coding ◽  
Genome Wide ◽  
De Novo Gene ◽  
The Impact ◽  
Transcribed Sequences

Abstract Mobile genetic Elements (MEs) are segments of DNA which can copy themselves and other transcribed sequences through the process of retrotransposition (RT). In humans several disorders have been attributed to RT, but the role of RT in severe developmental disorders (DD) has not yet been explored. Here we identify RT-derived events in 9738 exome sequenced trios with DD-affected probands. We ascertain 9 de novo MEs, 4 of which are likely causative of the patient’s symptoms (0.04%), as well as 2 de novo gene retroduplications. Beyond identifying likely diagnostic RT events, we estimate genome-wide germline ME mutation rate and selective constraint and demonstrate that coding RT events have signatures of purifying selection equivalent to those of truncating mutations. Overall, our analysis represents a comprehensive interrogation of the impact of retrotransposition on protein coding genes and a framework for future evolutionary and disease studies.

scholarly journals Telomeric DNA Mediates De Novo PML Body Formation

2009 ◽  
Vol 20 (22) ◽  
pp. 4804-4815 ◽  
Author(s):  
Anneke K. Brouwer ◽  
Joost Schimmel ◽  
Joop C.A.G. Wiegant ◽  
Alfred C.O. Vertegaal ◽  
Hans J. Tanke ◽  
...  
Keyword(s):  
De Novo ◽  
Cell Types ◽  
Promyelocytic Leukemia ◽  
Telomeric Dna ◽  
Body Formation ◽  
Cellular Processes ◽  
Sumo Ligase ◽  
Pml Bodies ◽  
Nuclear Processes

The cell nucleus harbors a variety of different bodies that vary in number, composition, and size. Although these bodies coordinate important nuclear processes, little is known about how they are formed. Among the most intensively studied bodies in recent years is the PML body. These bodies have been implicated in gene regulation and other cellular processes and are disrupted in cells from patients suffering from acute promyelocytic leukemia. Using live cell imaging microscopy and immunofluorescence, we show in several cell types that PML bodies are formed at telomeric DNA during interphase. Recent studies revealed that both SUMO modification sites and SUMO interaction motifs in the promyelocytic leukemia (PML) protein are required for PML body formation. We show that SMC5, a component of the SUMO ligase MMS21-containing SMC5/6 complex, localizes temporarily at telomeric DNA during PML body formation, suggesting a possible role for SUMO in the formation of PML bodies at telomeric DNA. Our data identify a novel role of telomeric DNA during PML body formation.

scholarly journals Adaptive Differences in Gene Expression in Farm-Impacted Seedbeds of the Native Blue Mussel Mytilus chilensis

2021 ◽  
Vol 12 ◽  
Author(s):  
Marco Yévenes ◽  
Gustavo Núñez-Acuña ◽  
Cristian Gallardo-Escárate ◽  
Gonzalo Gajardo
Keyword(s):  
Evolutionary Biology ◽  
De Novo ◽  
Blue Mussel ◽  
Fold Change ◽  
Genetic Determinants ◽  
Tissue Samples ◽  
Cellular Processes ◽  
Farming Industry ◽  
The Impact ◽  
Environmental Information Processing

The study of adaptive population differences is relevant for evolutionary biology, as it evidences the power of selective local forces relative to gene flow in maintaining adaptive phenotypes and their underlying genetic determinants. However, human-mediated hybridization through habitat translocations, a common and recurrent aquaculture practice where hybrids could eventually replace local genotypes, risk populations’ ability to cope with perturbations. The endemic marine mussel Mytilus chilensis supports a booming farming industry in the inner sea of Chiloé Island, southern Chile, which entirely relies on artificially collected seeds from natural beds that are translocated to ecologically different fattening centers. A matter of concern is how farm-impacted seedbeds will potentially cope with environmental shifts and anthropogenic perturbations. This study provides the first de novo transcriptome of M. chilensis; assembled from tissue samples of mantles and gills of individuals collected in ecologically different farm-impacted seedbeds, Cochamó (41°S) and Yaldad (43°S). Both locations and tissue samples differentially expressed transcripts (DETs) in candidate adaptive genes controlling multiple fitness traits, involved with metabolism, genetic and environmental information processing, and cellular processes. From 189,743 consensus contigs assembled: 1,716 (Bonferroni pvalue ≤ 0.05) were DETs detected in different tissues of samples from different locations, 210 of them (fold change ≥ | 100|) in the same tissue of samples from a different location, and 665 (fold change ≥ | 4|) regardless of the tissue in samples from a different location. Site-specific DETs in Cochamó (169) and Yaldad (150) in candidate genes controlling tolerance to temperature and salinity shifts, and biomineralization exhibit a high number of nucleotide genetic variants with regular occurrence (frequency > 99%). This novel M. chilensis transcriptome should help assessing and monitoring the impact of translocations in wild and farm-impacted mussel beds in Chiloé Island. At the same time, it would help designing effective managing practices for conservation, and translocation traceability.

scholarly journals De Novo Missense Mutations in TNNC1 and TNNI3 Causing Severe Infantile Cardiomyopathy Affect Myofilament Structure and Function and Are Modulated by Troponin Targeting Agents

2021 ◽  
Vol 22 (17) ◽  
pp. 9625
Author(s):  
Roua Hassoun ◽  
Heidi Budde ◽  
Hans Georg Mannherz ◽  
Mária Lódi ◽  
Setsuko Fujita-Becker ◽  
...  
Keyword(s):  
Molecular Mechanisms ◽  
Structural Integrity ◽  
Protein Quality ◽  
De Novo ◽  
Contractile Function ◽  
Regulatory Protein ◽  
Structural Defects ◽  
Similar Degree ◽  
Thin Filaments ◽  
The Impact

Rare pediatric non-compaction and restrictive cardiomyopathy are usually associated with a rapid and severe disease progression. While the non-compaction phenotype is characterized by structural defects and is correlated with systolic dysfunction, the restrictive phenotype exhibits diastolic dysfunction. The molecular mechanisms are poorly understood. Target genes encode among others, the cardiac troponin subunits forming the main regulatory protein complex of the thin filament for muscle contraction. Here, we compare the molecular effects of two infantile de novo point mutations in TNNC1 (p.cTnC-G34S) and TNNI3 (p.cTnI-D127Y) leading to severe non-compaction and restrictive phenotypes, respectively. We used skinned cardiomyocytes, skinned fibers, and reconstituted thin filaments to measure the impact of the mutations on contractile function. We investigated the interaction of these troponin variants with actin and their inter-subunit interactions, as well as the structural integrity of reconstituted thin filaments. Both mutations exhibited similar functional and structural impairments, though the patients developed different phenotypes. Furthermore, the protein quality control system was affected, as shown for TnC-G34S using patient’s myocardial tissue samples. The two troponin targeting agents levosimendan and green tea extract (-)-epigallocatechin-3-gallate (EGCg) stabilized the structural integrity of reconstituted thin filaments and ameliorated contractile function in vitro in some, but not all, aspects to a similar degree for both mutations.

scholarly journals Muscling in on mitochondrial sexual dimorphism; role of mitochondrial dimorphism in skeletal muscle health and disease

2017 ◽  
Vol 131 (15) ◽  
pp. 1919-1922 ◽  
Author(s):  
Gareth A. Nye ◽  
Giorgos K. Sakellariou ◽  
Hans Degens ◽  
Adam P. Lightfoot
Keyword(s):  
Skeletal Muscle ◽  
Sexual Dimorphism ◽  
Mitochondrial Function ◽  
Recent Article ◽  
Cellular Processes ◽  
Wide Range ◽  
Health And Disease ◽  
Muscle Health ◽  
The Impact

Mitochondria are no longer solely regarded as the cellular powerhouse; instead, they are now implicated in mediating a wide-range of cellular processes, in the context of health and disease. A recent article in Clinical Science, Ventura-Clapier et al. highlights the role of sexual dimorphism in mitochondrial function in health and disease. However, we feel the authors have overlooked arguably one of the most mitochondria-rich organs in skeletal muscle. Many studies have demonstrated that mitochondria have a central role in mediating the pathogenesis of myopathologies. However, the impact of sexual dimorphism in this context is less clear, with several studies reporting conflicting observations. For instance in ageing studies, a rodent model reported female muscles have higher antioxidant capacity compared with males; in contrast, human studies demonstrate no sex difference in mitochondrial bioenergetics and oxidative damage. These divergent observations highlight the importance of considering models and methods used to examine mitochondrial function, when interpreting these data. The use of either isolated or intact mitochondrial preparations in many studies appears likely to be a source of discord, when comparing many studies. Overall, it is now clear that more research is needed to determine if sexual dimorphism is a contributing factor in the development of myopathologies.

scholarly journals Impact of transposable elements on the genome of the urban malaria vector Anopheles coluzzii

2020 ◽  
Author(s):  
Carlos Vargas-Chavez ◽  
Neil Michel Longo Pendy ◽  
Sandrine E. Nsango ◽  
Laura Aguilera ◽  
Diego Ayala ◽  
...  
Keyword(s):  
Transposable Elements ◽  
Molecular Mechanisms ◽  
De Novo ◽  
Central Africa ◽  
Organic Pollution ◽  
Urban Environments ◽  
Sub Saharan Africa ◽  
Anopheles Coluzzii ◽  
The Impact

ABSTRACTBackgroundAnopheles coluzzii is one of the primary vectors of human malaria in sub-Saharan Africa. Recently, it has colonized the main cities of Central Africa threatening vector control programs. The adaptation of An. coluzzii to urban environments is partly due to an increased tolerance to organic pollution and insecticides. While some of the molecular mechanisms for ecological adaptation, including chromosome rearrangements and introgressions, are known, the role of transposable elements (TEs) in the adaptive processes of this species has not been studied yet.ResultsTo better understand the role of TEs in rapid urban adaptation, we sequenced using long-reads six An. coluzzii genomes from natural breeding sites in two major Central Africa cities. We de novo annotated the complete set of TEs and identified 64 previously undescribed families. TEs were non-randomly distributed throughout the genome with significant differences in the number of insertions of several superfamilies across the studied genomes. We identified seven putatively active families with insertions near genes with functions related to vectorial capacity. Moreover, we identified several TE insertions providing promoter and transcription factor binding sites to insecticide resistance and immune-related genes.ConclusionsThe analysis of multiple genomes sequenced using long-read technologies allowed us to generate the most comprehensive TE annotations in this species to date. We found that TEs have an impact in both the genome architecture and the regulation of functionally relevant genes in An. coluzzii. These results provide a basis for future studies of the impact of TEs on the biology of An. coluzzii.

scholarly journals The morphogenetic role of midline mesendoderm and ectoderm in the development of the forebrain and the midbrain of the mouse embryo

Development ◽  
2000 ◽  
Vol 127 (9) ◽  
pp. 1799-1813 ◽  
Author(s):  
A. Camus ◽  
B.P. Davidson ◽  
S. Billiards ◽  
P. Khoo ◽  
J.A. Rivera-Perez ◽  
...  
Keyword(s):  
Neural Tube ◽  
Mouse Embryo ◽  
De Novo ◽  
Gene Activity ◽  
Anteroposterior Patterning ◽  
De Novo Gene ◽  
Ventral Neural Tube ◽  
And Function ◽  
The Impact

The anterior midline tissue (AML) of the late gastrula mouse embryo comprises the axial mesendoderm and the ventral neuroectoderm of the prospective forebrain, midbrain and rostral hindbrain. In this study, we have investigated the morphogenetic role of defined segments of the AML by testing their inductive and patterning activity and by assessing the impact of their ablation on the patterning of the neural tube at the early-somite-stage. Both rostral and caudal segments of the AML were found to induce neural gene activity in the host tissue; however, the de novo gene activity did not show any regional characteristic that might be correlated with the segmental origin of the AML. Removal of the rostral AML that contains the prechordal plate resulted in a truncation of the head accompanied by the loss of several forebrain markers. However, the remaining tissues reconstituted Gsc and Shh activity and expressed the ventral forebrain marker Nkx2.1. Furthermore, analysis of Gsc-deficient embryos reveals that the morphogenetic function of the rostral AML requires Gsc activity. Removal of the caudal AML led to a complete loss of midline molecular markers anterior to the 4th somite. In addition, Nkx2.1 expression was not detected in the ventral neural tube. The maintenance and function of the rostral AML therefore require inductive signals emanating from the caudal AML. Our results point to a role for AML in the refinement of the anteroposterior patterning and morphogenesis of the brain.

scholarly journals Bearing My Heart: The Role of Extracellular Matrix on Cardiac Development, Homeostasis, and Injury Response

2021 ◽  
Vol 8 ◽  
Author(s):  
Ana Catarina Silva ◽  
Cassilda Pereira ◽  
Ana Catarina R. G. Fonseca ◽  
Perpétua Pinto-do-Ó ◽  
Diana S. Nascimento
Keyword(s):  
Extracellular Matrix ◽  
Cardiac Development ◽  
Cardiac Cells ◽  
Cellular Processes ◽  
Fibrotic Tissue ◽  
Short Period ◽  
And Function ◽  
Regenerative Therapies ◽  
The Impact

The extracellular matrix (ECM) is an essential component of the heart that imparts fundamental cellular processes during organ development and homeostasis. Most cardiovascular diseases involve severe remodeling of the ECM, culminating in the formation of fibrotic tissue that is deleterious to organ function. Treatment schemes effective at managing fibrosis and promoting physiological ECM repair are not yet in reach. Of note, the composition of the cardiac ECM changes significantly in a short period after birth, concurrent with the loss of the regenerative capacity of the heart. This highlights the importance of understanding ECM composition and function headed for the development of more efficient therapies. In this review, we explore the impact of ECM alterations, throughout heart ontogeny and disease, on cardiac cells and debate available approaches to deeper insights on cell–ECM interactions, toward the design of new regenerative therapies.

scholarly journals Depletion of the 110-Kilodalton Isoform of Poly(ADP-Ribose) Glycohydrolase Increases Sensitivity to Genotoxic and Endotoxic Stress in Mice

2004 ◽  
Vol 24 (16) ◽  
pp. 7163-7178 ◽  
Author(s):  
Ulrich Cortes ◽  
Wei-Min Tong ◽  
Donna L. Coyle ◽  
Mirella L. Meyer-Ficca ◽  
Ralph G. Meyer ◽  
...  
Keyword(s):  
Dna Damage ◽  
Alkylating Agents ◽  
Endotoxic Shock ◽  
Embryonic Stem ◽  
Cellular Processes ◽  
Streptozotocin Induced Diabetes ◽  
The Impact ◽  
Parp 1

ABSTRACT Poly(ADP-ribosylation) is rapidly stimulated in cells following DNA damage. This posttranslational modification is regulated by the synthesizing enzyme poly(ADP-ribose) polymerase 1 (PARP-1) and the degrading enzyme poly(ADP-ribose) glycohydrolase (PARG). Although the role of PARP-1 in response to DNA damage has been studied extensively, the function of PARG and the impact of poly(ADP-ribose) homeostasis in various cellular processes are largely unknown. Here we show that by gene targeting in embryonic stem cells and mice, we specifically deleted the 110-kDa PARG protein (PARG110) normally found in the nucleus and that depletion of PARG110 severely compromised the automodification of PARP-1 in vivo. PARG110-deficient mice were viable and fertile, but these mice were hypersensitive to alkylating agents and ionizing radiation. In addition, these mice were susceptible to streptozotocin-induced diabetes and endotoxic shock. These data indicate that PARG110 plays an important role in DNA damage responses and in pathological processes.

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