scholarly journals Conserved meiotic mechanisms in the cnidarian Clytia hemisphaerica revealed by Spo11 knockout

2022 ◽  
Author(s):  
Catriona Munro ◽  
Hugo Cadis ◽  
Evelyn Houliston ◽  
Jean-Ren&eacute Huynh

During meiosis, each duplicated chromosome pairs and recombines with its unique homolog to ensure the shuffling of genetic information across generations. Functional studies in classical model organisms have revealed a surprising diversity in the chronology and interdependency of the earliest meiotic steps such as chromosome movements, pairing, association via Synaptonemal Complex formation (synapsis), recombination and the formation of chiasmata. A key player is Spo11, an evolutionarily conserved topoisomerase-related transesterase that initiates meiotic recombination via the catalysis of programmed DNA double stranded breaks (DSBs). While DSBs are required for pairing and synapsis in budding yeast and mouse, alternative pathways are employed during female meiosis of the fruit fly and nematode Caenorhabditis elegans. Here, to provide a comparative perspective on meiotic regulation from a distinct animal clade, we chart gametogenesis in Clytia hemisphaerica jellyfish and examine the role of Spo11 using CRISPR-Cas9 mutants, generated clonally from F0 polyp colonies. Spo11 mutant females fail to assemble synaptonemal complexes and chiasmata, such that homologous chromosome pairs disperse during oocyte growth. Subsequent meiotic divisions are abnormal but produce viable progeny. Clytia thus shares an ancient eukaryotic dependence of synapsis and chromosome segregation on Spo11-generated DSBs. It provides a valuable additional experimental model for dissecting meiotic mechanisms during animal gametogenesis, and for building a comparative framework for distinguishing evolutionarily conserved versus flexible features of meiosis.

2020 ◽  
Vol 8 (2) ◽  
pp. 10
Author(s):  
Michael T. Chin ◽  
Simon J. Conway

Tafazzin, an enzyme associated with the rare inherited x-linked disorder Barth Syndrome, is a nuclear encoded mitochondrial transacylase that is highly conserved across multiple species and plays an important role in mitochondrial function. Numerous studies have elucidated the mechanisms by which Tafazzin affects mitochondrial function, but its effects on development and susceptibility to adult disease are incompletely understood. The purpose of this review is to highlight previous functional studies across a variety of model organisms, introduce recent studies that show an important role in development, and also to provide an update on the role of Tafazzin in human disease. The profound effects of Tafazzin on cardiac development and adult cardiac homeostasis will be emphasized. These studies underscore the importance of mitochondrial function in cardiac development and disease, and also introduce the concept of Tafazzin as a potential therapeutic modality.


2020 ◽  
Vol 21 (6) ◽  
pp. 2002 ◽  
Author(s):  
Darcy C. Engelhart ◽  
Priti Azad ◽  
Suwayda Ali ◽  
Jeffry C. Granados ◽  
Gabriel G. Haddad ◽  
...  

The SLC22 family of transporters is widely expressed, evolutionarily conserved, and plays a major role in regulating homeostasis by transporting small organic molecules such as metabolites, signaling molecules, and antioxidants. Analysis of transporters in fruit flies provides a simple yet orthologous platform to study the endogenous function of drug transporters in vivo. Evolutionary analysis of Drosophila melanogaster putative SLC22 orthologs reveals that, while many of the 25 SLC22 fruit fly orthologs do not fall within previously established SLC22 subclades, at least four members appear orthologous to mammalian SLC22 members (SLC22A16:CG6356, SLC22A15:CG7458, CG7442 and SLC22A18:CG3168). We functionally evaluated the role of SLC22 transporters in Drosophila melanogaster by knocking down 14 of these genes. Three putative SLC22 ortholog knockdowns—CG3168, CG6356, and CG7442/SLC22A—did not undergo eclosion and were lethal at the pupa stage, indicating the developmental importance of these genes. Additionally, knocking down four SLC22 members increased resistance to oxidative stress via paraquat testing (CG4630: p < 0.05, CG6006: p < 0.05, CG6126: p < 0.01 and CG16727: p < 0.05). Consistent with recent evidence that SLC22 is central to a Remote Sensing and Signaling Network (RSSN) involved in signaling and metabolism, these phenotypes support a key role for SLC22 in handling reactive oxygen species.


2012 ◽  
Vol 53 ◽  
pp. 129-140 ◽  
Author(s):  
Daniel T. Bergstralh ◽  
Daniel St Johnston

Epithelial cells are polarized along their apical–basal axis. Much of the cellular machinery that goes into establishing and maintaining epithelial cell polarity is evolutionarily conserved. Model organisms, including the fruit fly, Drosophila melanogaster, are thus particularly useful for the study of cell polarity. Work in Drosophila has identified several important components of the polarity machinery and has also established the surprising existence of a secondary cell polarity pathway required only under conditions of energetic stress. This work has important implications for the understanding of human cancer. Most cancers are epithelial in origin, and the loss of cell polarity is a critical step towards malignancy. Thus a better understanding of how polarity is established and maintained in epithelial cells will help us to understand the process of malignant transformation and may lead to improved therapies. In the present chapter we discuss the current understanding of how epithelial cell polarity is regulated and the known associations between polarity factors and cancer.


Biomolecules ◽  
2022 ◽  
Vol 12 (1) ◽  
pp. 125
Author(s):  
Abhinav B. Swaminathan ◽  
Vishal M. Gohil

Copper is essential for the stability and activity of cytochrome c oxidase (CcO), the terminal enzyme of the mitochondrial respiratory chain. Copper is bound to COX1 and COX2, two core subunits of CcO, forming the CuB and CuA sites, respectively. Biogenesis of these two copper sites of CcO occurs separately and requires a number of evolutionarily conserved proteins that form the mitochondrial copper delivery pathway. Pathogenic mutations in some of the proteins of the copper delivery pathway, such as SCO1, SCO2, and COA6, have been shown to cause fatal infantile human disorders, highlighting the biomedical significance of understanding copper delivery mechanisms to CcO. While two decades of studies have provided a clearer picture regarding the biochemical roles of SCO1 and SCO2 proteins, some discrepancy exists regarding the function of COA6, the new member of this pathway. Initial genetic and biochemical studies have linked COA6 with copper delivery to COX2 and follow-up structural and functional studies have shown that it is specifically required for the biogenesis of the CuA site by acting as a disulfide reductase of SCO and COX2 proteins. Its role as a copper metallochaperone has also been proposed. Here, we critically review the recent literature regarding the molecular function of COA6 in CuA biogenesis.


2020 ◽  
Vol 48 (2) ◽  
pp. 367-377 ◽  
Author(s):  
Claudia Lennicke ◽  
Helena M. Cochemé

Ageing and age-related diseases are major challenges for the social, economic and healthcare systems of our society. Amongst many theories, reactive oxygen species (ROS) have been implicated as a driver of the ageing process. As by-products of aerobic metabolism, ROS are able to randomly oxidise macromolecules, causing intracellular damage that accumulates over time and ultimately leads to dysfunction and cell death. However, the genetic overexpression of enzymes involved in the detoxification of ROS or treatment with antioxidants did not generally extend lifespan, prompting a re-evaluation of the causal role for ROS in ageing. More recently, ROS have emerged as key players in normal cellular signalling by oxidising redox-sensitive cysteine residues within proteins. Therefore, while high levels of ROS may be harmful and induce oxidative stress, low levels of ROS may actually be beneficial as mediators of redox signalling. In this context, enhancing ROS production in model organisms can extend lifespan, with biological effects dependent on the site, levels, and specific species of ROS. In this review, we examine the role of ROS in ageing, with a particular focus on the importance of the fruit fly Drosophila as a powerful model system to study redox processes in vivo.


2014 ◽  
Vol 2014 ◽  
pp. 1-24 ◽  
Author(s):  
Nitha C. Mulakkal ◽  
Peter Nagy ◽  
Szabolcs Takats ◽  
Radu Tusco ◽  
Gábor Juhász ◽  
...  

The discovery of evolutionarily conserved Atg genes required for autophagy in yeast truly revolutionized this research field and made it possible to carry out functional studies on model organisms. Insects includingDrosophilaare classical and still popular models to study autophagy, starting from the 1960s. This review aims to summarize past achievements and our current knowledge about the role and regulation of autophagy inDrosophila, with an outlook to yeast and mammals. The basic mechanisms of autophagy in fruit fly cells appear to be quite similar to other eukaryotes, and the role that this lysosomal self-degradation process plays inDrosophilamodels of various diseases already made it possible to recognize certain aspects of human pathologies. Future studies in this complete animal hold great promise for the better understanding of such processes and may also help finding new research avenues for the treatment of disorders with misregulated autophagy.


Biomolecules ◽  
2020 ◽  
Vol 10 (7) ◽  
pp. 985
Author(s):  
Jose L. Salazar ◽  
Sheng-An Yang ◽  
Shinya Yamamoto

Since its discovery in Drosophila, the Notch signaling pathway has been studied in numerous developmental contexts in diverse multicellular organisms. The role of Notch signaling in nervous system development has been extensively investigated by numerous scientists, partially because many of the core Notch signaling components were initially identified through their dramatic ‘neurogenic’ phenotype of developing fruit fly embryos. Components of the Notch signaling pathway continue to be expressed in mature neurons and glia cells, which is suggestive of a role in the post-developmental nervous system. The Notch pathway has been, so far, implicated in learning and memory, social behavior, addiction, and other complex behaviors using genetic model organisms including Drosophila and mice. Additionally, Notch signaling has been shown to play a modulatory role in several neurodegenerative disease model animals and in mediating neural toxicity of several environmental factors. In this paper, we summarize the knowledge pertaining to the post-developmental roles of Notch signaling in the nervous system with a focus on discoveries made using the fruit fly as a model system as well as relevant studies in C elegans, mouse, rat, and cellular models. Since components of this pathway have been implicated in the pathogenesis of numerous psychiatric and neurodegenerative disorders in human, understanding the role of Notch signaling in the mature brain using model organisms will likely provide novel insights into the mechanisms underlying these diseases.


2021 ◽  
Vol 18 (1) ◽  
Author(s):  
Daniel K. Fabian ◽  
Matías Fuentealba ◽  
Handan Melike Dönertaş ◽  
Linda Partridge ◽  
Janet M. Thornton

AbstractAt first glance, longevity and immunity appear to be different traits that have not much in common except the fact that the immune system promotes survival upon pathogenic infection. Substantial evidence however points to a molecularly intertwined relationship between the immune system and ageing. Although this link is well-known throughout the animal kingdom, its genetic basis is complex and still poorly understood. To address this question, we here provide a compilation of all genes concomitantly known to be involved in immunity and ageing in humans and three well-studied model organisms, the nematode worm Caenorhabditis elegans, the fruit fly Drosophila melanogaster, and the house mouse Mus musculus. By analysing human orthologs among these species, we identified 7 evolutionarily conserved signalling cascades, the insulin/TOR network, three MAPK (ERK, p38, JNK), JAK/STAT, TGF-β, and Nf-κB pathways that act pleiotropically on ageing and immunity. We review current evidence for these pathways linking immunity and lifespan, and their role in the detrimental dysregulation of the immune system with age, known as immunosenescence. We argue that the phenotypic effects of these pathways are often context-dependent and vary, for example, between tissues, sexes, and types of pathogenic infection. Future research therefore needs to explore a higher temporal, spatial and environmental resolution to fully comprehend the connection between ageing and immunity.


2009 ◽  
Vol 418 (1) ◽  
pp. 1-12 ◽  
Author(s):  
Susan Broughton ◽  
Linda Partridge

Enormous strides in understanding aging have come from the discovery that mutations in single genes can extend healthy life-span in laboratory model organisms such as the yeast Saccharomyces, the fruit fly Drosophila melanogaster, the nematode worm Caenorhabditis elegans and the mouse. IIS [insulin/IGF (insulin-like growth factor)-like signalling] stands out as an important, evolutionarily conserved pathway involved in the determination of lifespan. The pathway has diverse functions in multicellular organisms, and mutations in IIS can affect growth, development, metabolic homoeostasis, fecundity and stress resistance, as well as lifespan. The pleiotropic nature of the pathway and the often negative effects of its disruption mean that the extent, tissue and timing of IIS manipulations are determinants of a positive effect on lifespan. One tissue of particular importance for lifespan extension in diverse organisms is the CNS (central nervous system). Although lowered IIS in the CNS can extend lifespan, IIS is also widely recognized as being neuroprotective and important for growth and survival of neurons. In the present review, we discuss our current understanding of the role of the nervous system in extension of lifespan by altered IIS, and the role of IIS in determination of neuronal function during aging. The nervous system can play both endocrine and cell-autonomous roles in extension of lifespan by IIS, and the effects of IIS on lifespan and neuronal function can be uncoupled to some extent. Tissue-specific manipulation of IIS and the cellular defence mechanisms that it regulates will better define the ways in which IIS affects neuronal and whole-organism function during aging.


Author(s):  
Ann LeFurgey ◽  
Peter Ingram ◽  
J.J. Blum ◽  
M.C. Carney ◽  
L.A. Hawkey ◽  
...  

Subcellular compartments commonly identified and analyzed by high resolution electron probe x-ray microanalysis (EPXMA) include mitochondria, cytoplasm and endoplasmic or sarcoplasmic reticulum. These organelles and cell regions are of primary importance in regulation of cell ionic homeostasis. Correlative structural-functional studies, based on the static probe method of EPXMA combined with biochemical and electrophysiological techniques, have focused on the role of these organelles, for example, in maintaining cell calcium homeostasis or in control of excitation-contraction coupling. New methods of real time quantitative x-ray imaging permit simultaneous examination of multiple cell compartments, especially those areas for which both membrane transport properties and element content are less well defined, e.g. nuclei including euchromatin and heterochromatin, lysosomes, mucous granules, storage vacuoles, microvilli. Investigations currently in progress have examined the role of Zn-containing polyphosphate vacuoles in the metabolism of Leishmania major, the distribution of Na, K, S and other elements during anoxia in kidney cell nuclel and lysosomes; the content and distribution of S and Ca in mucous granules of cystic fibrosis (CF) nasal epithelia; the uptake of cationic probes by mltochondria in cultured heart ceils; and the junctional sarcoplasmic retlculum (JSR) in frog skeletal muscle.


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