* Your assessment is very important for improving the workof artificial intelligence, which forms the content of this project
Download Sager JJ, Bai Q, Burton EA
Ridge (biology) wikipedia , lookup
Gene therapy of the human retina wikipedia , lookup
Genomic imprinting wikipedia , lookup
Heritability of IQ wikipedia , lookup
Genome evolution wikipedia , lookup
Behavioural genetics wikipedia , lookup
Minimal genome wikipedia , lookup
Polycomb Group Proteins and Cancer wikipedia , lookup
Quantitative trait locus wikipedia , lookup
Human genetic variation wikipedia , lookup
Medical genetics wikipedia , lookup
Artificial gene synthesis wikipedia , lookup
Epigenetics of human development wikipedia , lookup
Genetic engineering wikipedia , lookup
Mir-92 microRNA precursor family wikipedia , lookup
Epigenetics of neurodegenerative diseases wikipedia , lookup
Gene expression profiling wikipedia , lookup
History of genetic engineering wikipedia , lookup
Gene expression programming wikipedia , lookup
Nutriepigenomics wikipedia , lookup
Biology and consumer behaviour wikipedia , lookup
Site-specific recombinase technology wikipedia , lookup
Microevolution wikipedia , lookup
Designer baby wikipedia , lookup
Review Linking genes to brain, behavior and neurological diseases: what can we learn from zebrafish? S. Guo How our brain is wired and subsequently generates functional output, ranging from sensing and locomotion to emotion, decision-making and learning and memory, remains poorly understood. Dys-regulation of these processes can lead to neurodegenerative, as well as neuropsychiatric, disorders. Molecular genetic together with behavioral analyses in model organisms identify genes involved in the formation of neuronal circuits, the execution of behavior and mechanisms involved in neuropathogenesis. In this review I will discuss the current progress and future potential for study in a newly established vertebrate model organism for genetics, the zebrafish Danio rerio. Where available, schemes and results of genetic screens will be reviewed concerning the sensory, motor and neuromodulatory monoamine systems. Genetic analyses in zebrafish have the potential to provide important insights into the relationship between genes, neuronal circuits and behavior in normal as well as diseased states. PENTYLENETETRAZOLE INDUCED CHANGES IN ZEBRAFISH BEHAVIOR, NEURAL ACTIVITY AND C-FOS EXPRESSION] S. C. BARABAN,a* M. R. TAYLOR,a P. A. CASTRO,a AND H. BAIERb Abstract—Rodent seizure models have significantly contributed to our basic understanding of epilepsy. However, medically intractable forms of epilepsy persist and the fundamental mechanisms underlying this disease remain unclear. Here we show that seizures can be elicited in a simple vertebrate system e.g. zebrafish larvae (Danio rerio). Exposure to a common convulsant agent (pentylenetetrazole, PTZ) induced a stereotyped and concentration-dependent sequence of behavioral changes culminating in clonus-like convulsions. Extracellular recordings from fish optic tectum revealed ictal and interictal-like electrographic discharges after application of PTZ, which could be blocked by tetrodotoxin or glutamate receptor antagonists. Epileptiform discharges were suppressed by commonly used antiepileptic drugs, valproate and diazepam, in a concentration-dependent manner. Upregulation of c-fos expression was also observed in CNS structures of zebrafish exposed to PTZ. Taken together, these results demonstrate that chemically-induced seizures in zebrafish exhibit behavioral, electrographic, and molecular changes that would be expected from a rodent seizure model. Therefore, zebrafish larvae represent a powerful new system to study the underlying basis of seizure generation, epilepsy and epileptogenesis. FishNet: an online database of zebrafish anatomy Robert J Bryson-Richardson*1, Silke Berger1, Thomas F Schilling2, Thomas E Hall1, Nicholas J Cole1, Abigail J Gibson1, James Sharpe3 and Peter D Currie*1,4,5 Abstract Background: Over the last two decades, zebrafish have been established as a genetically versatile model system for investigating many different aspects of vertebrate developmental biology. With the credentials of zebrafish as a developmental model now well recognized, the emerging new opportunity is the wider application of zebrafish biology to aspects of human disease modelling. This rapidly increasing use of zebrafish as a model for human disease has necessarily generated interest in the anatomy of later developmental phases such as the larval, juvenile, and adult stages, during which many of the key aspects of organ morphogenesis and maturation take place. Anatomical resources and references that encompass these stages are non-existent in zebrafish and there is therefore an urgent need to understand how different organ systems and anatomical structures develop throughout the life of the fish. Results: To overcome this deficit we have utilized the technique of optical projection tomography to produce three-dimensional (3D) models of larval fish. In order to view and display these models we have created FishNet http://www.fishnet.org.au, an interactive reference of zebrafish anatomy spanning the range of zebrafish development from 24 h until adulthood. Conclusion: FishNet contains more than 36 000 images of larval zebrafish, with more than 1 500 of these being annotated. The 3D models can be manipulated on screen or virtually sectioned. This resource represents the first complete embryo to adult atlas for any species in 3D. http://books.google.com.br/books?hl=ptBR&lr=&id=Qw6KqLjwtZQC&oi=fnd&pg=PA189&dq=zebrafish+as+a+model+for+studying+g enetic+aspects+of+epilepsy&ots=Dd1W_wDOPb&sig=ijO0spDlj9Q992rmHAE7ceFqWSw#v =onepage&q&f=false (Modeling epilepsy and seizures in developing zebrafish larvae) (nao foi possivel copiar e colar o texto, disponivel no site) Scott Baraban Letter Zebrafish, Killifish, Neither Fish, Both Fish? Glenn S. Gerhard Weis Center for Research Danville, Pennsylvania Renae L. Malek The Institute for Genomic Research Rockville, Maryland Evan Keller Jill Murtha Departments of Urology and Pathology University of Michigan Ann Arbor Keith C. Cheng Jake Gittlen Cancer Research Institute Department of Pathology Pennsylvania State College of Medicine Hershey In their recent report (1), Herrera and Jagadeeswaran offer data supporting the use of killifish (annual fish) species over zebrafish as a genetic model for aging. We write to emphasize that, despite the limitations that killifish may circumvent, the zebrafish holds great promise as a model for aging research (2). In gerontology, as well as in other fields, a variety of model systems are used to a collective advantage. For each system, its inevitable disadvantages do not invalidate the exploitation of its advantages. For example, despite the inability to develop cancer, important cancer-related research continues to be conducted in yeast (3). Similarly, Caenorhabditis elegans is widely used in gerontology despite the lack of cell division potential in somatic cells of adults. No model is perfect, and based upon its numerous experimental advantages and its track record, the zebrafish should receive serious consideration in any area of biology. THE ZEBRAFISH AS A MODEL FOR HUMAN DISEASE William T. Penberthy, Ebrahim Shafizadeh, and Shuo Lin 1. ABSTRACT Much of our current understanding of the function of genes modulating the normal process of embryonic development has come from mutant analysis. The availability of thousands of mutant lines in zebrafish that allows for identification of novel genes regulating various aspects of embryogenesis has been instrumental in establishing zebrafish as a robust and reliable genetic system. With the advances in genomic sequencing, the construction of several genetic maps, and cloning of hundreds of ESTs, positional cloning experiments in zebrafish have become more approachable. An increasing number of mutant genes have been cloned. Several zebrafish mutants are representative of known forms of human genetic diseases. The success of morpholino antisense technology in zebrafish potentially opens the door for modeling nearly any inherited developmental defect. This review highlights the strengths and limitations of using the zebrafish as an organism for elucidation of the genetic etiology of human disease. Additionally a survey of current and future zebrafish models of human disease is presented. Spontaneous Seizures and Altered Gene Expression in GABA Signaling Pathways in a mind bomb Mutant Zebrafish Hortopan GA, Dinday MT, Baraban SC. Abstract Disruption of E3 ubiquitin ligase activity in immature zebrafish mind bomb mutants leads to a failure in Notch signaling, excessive numbers of neurons, and depletion of neural progenitor cells. This neurogenic phenotype is associated with defects in neural patterning and brain development. Because developmental brain abnormalities are recognized as an important feature of childhood neurological disorders such as epilepsy and autism, we determined whether zebrafish mutants with grossly abnormal brain structure exhibit spontaneous electrical activity that resembles the long-duration, high-amplitude multispike discharges reported in immature zebrafish exposed to convulsant drugs. Electrophysiological recordings from agar immobilized mind bomb mutants at 3 d postfertilization confirmed the occurrence of electrographic seizure activity; seizure-like behaviors were also noted during locomotion video tracking of freely behaving mutants. To identify genes differentially expressed in the mind bomb mutant and provide insight into molecular pathways that may mediate these epileptic phenotypes, a transcriptome analysis was performed using microarray. Interesting candidate genes were further analyzed using conventional reverse transcriptase-PCR and real-time quantitative PCR, as well as wholemount in situ hybridization. Approximately 150 genes, some implicated in development, transcription, cell metabolism, and signal transduction, are differentially regulated, including downregulation of several genes necessary for GABA-mediated signaling. These findings identify a collection of gene transcripts that may be responsible for the abnormal electrical discharge and epileptic activities observed in a mind bomb zebrafish mutant. This work may have important implications for neurological and neurodevelopmental disorders associated with mutations in ubiquitin ligase activity. A large-scale mutagenesis screen to identify seizure-resistant zebrafish. Baraban SC, Dinday MT, Castro PA, Chege S, Guyenet S, Taylor MR Summary: Purpose: Zebrafish are a vertebrate organism ideally suited to mutagenesis screening strategies. Although a genetic basis for seizure susceptibility and epilepsy is well established, no efforts have been made to study seizure resistance. Here we describe a novel strategy to isolate seizure-resistant zebrafish mutants from a large-scale mutagenesis screen. Methods: Seizures were induced with pentylenetetrazole (PTZ). Zebrafish were analyzed between 3 and 7 days postfertilization (dpf). Genome mutations were induced in founders by using N-ethyl-nitrosourea (ENU). Seizure behavior was monitored by using a high-speed camera and quantified by locomotiontracking software. Electrographic activity was monitored by using a field-recording electrode placed in the optic tectum of agarimmobilized zebrafish. Results: Short-term PTZ exposure elicited a burst-suppression seizure pattern in 3-dpf zebrafish and more complex activity consisting of interictal- and ictal-like discharges at 7 dpf. Prolonged exposure to PTZ induced status epilepticus–like seizure activity and fatality in wild-type zebrafish larvae. With a PTZ survival assay at 6–7 dpf, we identified six zebrafish mutants in a forward-genetic screen covering nearly 2,000 F2 families. One mutant (s334) also was shown to exhibit reduced behavioral activity on short-term PTZ exposure and an inability to generate long-duration ictal-like discharge. Conclusions: Zebrafish offers a powerful tool for the identification and study of a genetic basis for seizure resistance. Key Words: Seizure—PTZ—Mutagenesis— Electrophysiology—Forward genetics—Screen—Behavior. Zebrafish as a Simple Vertebrate Organism for Epilepsy Research (3 paginas disponiveis do livro no site- Scott Barabanhttp://www.springerlink.com/content/r788763k17066570/#section=67445&page=1) Review Transgenic zebrafish models of neurodegenerative diseases Sager JJ, Bai Q, Burton EA Abstract Since the introduction of the zebrafish as a model for the study of vertebrate developmental biology, an extensive array of techniques for its experimental manipulation and analysis has been developed. Recently it has become apparent that these powerful methodologies might be deployed in order to elucidate the pathogenesis of human neurodegenerative diseases and to identify candidate therapeutic approaches. In this article, we consider evidence that the zebrafish central nervous system provides an appropriate setting in which to model human neurological disease and we review techniques and resources available for generating transgenic models. We then examine recent publications showing that appropriate phenotypes can be provoked in the zebrafish through transgenic manipulations analogous to genetic abnormalities known to cause human tauopathies, polyglutamine diseases or motor neuron degenerations. These studies show proof of concept that findings in zebrafish models can be applicable to the pathogenic mechanisms underlying human diseases. Consequently, the prospects for providing novel insights into neurodegenerative diseases by exploiting transgenic zebrafish models and discovery-driven approaches seem favorable. THE ZEBRAFISH SCIENCE MONITOR CHARACTERIZATION OF A CELL LINE DERIVED FROM ZEBRAFISH (BRACHYDANIO RERIO) EMBRYOS By Wolfgang Driever and Zehava Rangini; Cardiovascular Research Center, Massachusetts General Hospital, 149 Thirteenth St., Charlestown, MA 02129, USA During the last decade, zebrafish (Brachydanio rerio) have emerged as a novel and attractive system to study embryogenesis and organogenesis in vertebrates. The main reason is that both extensive genetic studies and detailed embryological analysis are possible using this small tropical fresh water teleost. However, in vitro analysis using cell culture or molecular genetics are still far less advanced than in other vertebrate systems. We report the generation and characterization of a fibroblast like cell line, ZF4, derived from one day old zebrafish embryos. The hyperploid cell line has been stable in multiple passages for more than two years now and is the first zebrafish cell line that can be maintained in conventional medium containing mammalian serum. Using a series of plasmids for expression of a marker gene, we evaluate in ZF4 cells the relative strength of expression from several different viral, fish and mammalian promoters. Stable integration can be obtained by using G418 selection. We hope that our cell line will be a useful tool for the analysis of gene regulation in zebrafish Using Gene-History and Expression Analyses to Assess the Involvement of LGI Genes in Human Disorders Gu W, Gibert Y, Wirth T, Elischer A, Bloch W, Meyer A, Steinlein OK, Begemann G Abstract Mutations in the leucine-rich, glioma-inactivated 1 gene, LGI1, cause autosomal-dominant lateral temporal lobe epilepsy via unknown mechanisms. LGI1 belongs to a subfamily of leucine-rich repeat genes comprising four members (LGI1–LGI4) in mammals. In this study, both comparative developmental as well as molecular evolutionary methods were applied to investigate the evolution of the LGI gene family and, subsequently, of the functional importance of its different gene members. Our phylogenetic studies suggest that LGI genes evolved early in the vertebrate lineage. Genetic and expression analyses of all five zebrafish lgi genes revealed duplications of lgi1 and lgi2, each resulting in two paralogous gene copies with mostly nonoverlapping expression patterns. Furthermore, all vertebrate LGI1 orthologs experience high levels of purifying selection that argue for an essential role of this gene in neural development or function. The approach of combining expression and selection data used here exemplarily demonstrates that in poorly characterized gene families a framework of evolutionary and expression analyses can identify those genes that are functionally most important and are therefore prime candidates for human disorders. A FISHY EPILEPSY MODEL by Jack Parent, MD COMMENTARY Research into epilepsy mechanisms primarily involves studies of rodents. Other mammalian species are occasionally investigated, as is mammalian tissue grown as individual neural cells or brain slices in the dish. Simpler vertebrates have not been used as model systems to study epilepsy. Many argue that their nervous systems are too primitive to generate seizures or that potential seizure-like activity in these models has little relevance to human epilepsy. The conservation of many neural functions among vertebrates, however, suggests that fish and other simpler vertebrates may provide useful models for a variety of neurological disorders. Indeed, studies of simpler vertebrates, such as zebrafish, have shed light on brain developmental mechanisms in mammals. In this regard, Baraban and colleagues examine the feasibility of using developing zebrafish larvae as an epilepsy model system.