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[
Dev Cell,
2005]
The neuron is a prime example of a highly polarized cell. It is becoming clear that conserved protein complexes, which have been shown to regulate polarity in such diverse systems as the C. elegans zygote and mammalian epithelia, are also required for neuronal polarization. This review considers the role of these polarity proteins in axon specification and synapto-genesis.
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Cell,
1996]
Anyone who has watched an early embryo develop cannot help but be awed by the choreography of the early cleavages. The orientation and timing of cleavage in an animal cell are always such that the cleavage furrow bisects the mitotic apparatus (MA) during telophase, thus ensuring the equal partitioning of daughter chromosomes. In addition, the regulation of cleavage plane orientation is necessary for correct partitioning of localized determinants to specific daughter cells, for optimal positioning of cells in developing embryos, and for morphogenesis in plants, which are not motile.
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Curr Opin Cell Biol,
2013]
With its invariant cell lineage, easy genetics and small genome, the nematode Caenorhabditis elegans has emerged as one of the prime models in developmental biology over the last 50 years. Surprisingly however, until a decade ago very little was known about nuclear organization in worms, even though it is an ideal model system to explore the link between nuclear organization and cell fate determination. Here, we review the latest findings that exploit the repertoire of genetic tools developed in worms, leading to the identification of important sequences and signals governing the changes in chromatin tridimensional architecture. We also highlight parallels and differences to other model systems.
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Curr Opin Neurobiol,
2002]
Advances in the study of Drosophila melanogaster and Caenorhabditis elegans have provided key insights into the processes of neurotransmission and neuromodulation. Work in the past year has revealed that Unc-13 and Rab3a-interacting molecule regulate the conformational state of syntaxin to prime synaptic vesicle fusion. Analyses of synaptotagmin support its role as a putative calcium sensor triggering vesicular fusion and highlight the possible role of SNARE complex oligomerization in the fusion mechanism. Characterization of endophilin mutants demonstrates that kiss-and-run endocytosis is a major component of synaptic vesicle recycling. In neuromodulation, dcaps mutants provide the first genetic insight into possible roles of the CAPS protein in mediating dense core vesicle fusion and modulating synaptic
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Bioessays,
1992]
It is somewhat ironic that animals that are the prime choice for detailed genetic analysis, such as the fruit fly and the nematode, have thus far been largely refractory to reverse genetic analysis. Their detailed genetic map, and small genome size have made them subjects of ambitious genome analysis projects, but there is still no strategy to introduce desired changes into their genomes by homologous recombination. Some alternative approaches have recently become available; this review describes possibilities and unsolved problems for reverse genetics in the nematode Caenorhabditis elegans. The transposon Tc1 could prove to be very useful for the isolation of knock out mutants, and possibly also for introduction of more subtle alterations.
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Drug Discov Today Technol,
2013]
Alzheimer's disease (AD) is a complex human neurodegenerative disease. Currently the therapeutics for AD only treats the symptoms. While numbers of excellent studies have used mammalian models to discover new compounds, the time and effort involved with screening large numbers of candidates is prohibitive. Cultured mammalian neurons are often used to perform high-throughput screens (HTS); however, cell culture lacks the organismal complexity involved in AD. To address these issues several researchers are turning to the roundworm, Caenorhabditis elegans. C. elegans has numerous models of both Tau and Ab induced toxicity, the two prime components observed to correlate with AD pathology. These models have led to the discovery of numerous AD modulating candidates. Further, the ease of performing RNA interference for any gene in the C. elegans genome allows for identification of proteins involved in the mechanism of drug action. These attributes make C. elegans well positioned to aid in the discovery of new AD therapies.
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WormBook,
2010]
The nervous system represents the most complex tissue of C. elegans both in terms of numbers (302 neurons and 56 glial cells = 37% of the somatic cells in a hermaphrodite) and diversity (118 morphologically distinct neuron classes). The lineage and morphology of each neuron type has been described in detail and neuronal fate markers exists for virtually all neurons in the form of fluorescent reporter genes. The ability to "phenotype" neurons at high resolution combined with the amenability of C. elegans to genetic mutant analysis make the C. elegans nervous system a prime model system to elucidate the nature of the gene regulatory programs that build a nervous system-a central question of developmental neurobiology. Discussing a number of regulatory genes involved in neuronal lineage determination and neuronal differentiation, I will try to carve out in this review a few general principles of neuronal development in C. elegans. These principles may be conserved across phylogeny.
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Front Cell Neurosci,
2013]
Left-right asymmetry in anatomical structures and functions of the nervous system is present throughout the animal kingdom. For example, language centers are localized in the left side of the human brain, while spatial recognition functions are found in the right hemisphere in the majority of the population. Disruption of asymmetry in the nervous system is correlated with neurological disorders. Although anatomical and functional asymmetries are observed in mammalian nervous systems, it has been a challenge to identify the molecular basis of these asymmetries. C. elegans has emerged as a prime model organism to investigate molecular asymmetries in the nervous system, as it has been shown to display functional asymmetries clearly correlated to asymmetric distribution and regulation of biologically relevant molecules. Small non-coding RNAs have been recently implicated in various aspects of neural development. Here, we review cases in which microRNAs are crucial for establishing left-right asymmetries in the C. elegans nervous system. These studies may provide insight into how molecular and functional asymmetries are established in the human brain.
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Science,
1998]
The Caenorhabditis elegans genome sequence was surveyed for transcription factor and signaling gene families that have been shown to regulate development in a variety of species. About 10 to 25 percent of the genes in most of the gene families already have been genetically analyzed in C. elegans, about half of the genes detect probable orthologs in other species, and about 10 to 25 percent of the genes are, at present, unique to C. elegans. Caenorhabditis elegans is also missing genes that are found in vertebrates and other invertebrates. Thus the genome sequence reveals universals in developmental control that are the legacy of metazoan complexity before the Cambrian explosion, as well as genes that have been more recently invented or lost in particular phylogenetic lineages.AD - Department of Molecular Biology, Massachusetts General Hospital, Department of Genetics, Harvard Medical School, Boston, MA 02114, USA. ruvkun@frodo.mgh.harvard.eduFAU - Ruvkun, GAU - Ruvkun GFAU - Hobert, OAU - Hobert OLA - engPT - Journal ArticlePT - ReviewPT - Review, TutorialCY - UNITED STATESTA - ScienceJID - 0404511RN - 0 (Helminth Proteins)RN - 0 (Transcription Factors)SB - IM
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Biomed Res Int,
2015]
Ultimately, the production of new proteins in undetermined cells pushes them to new fates. Other proteins hold a stem cell in a mode of self-renewal. In germ cells, these decision-making proteins are produced largely from translational control of preexisting mRNAs. To date, all of the regulation has been attributed to RNA binding proteins (RBPs) that repress mRNAs in many models of germ cell development (Drosophila, mouse, C. elegans, and Xenopus). In this review, we focus on the selective, positive function of translation initiation factors eIF4E and eIF4G, which recruit mRNAs to ribosomes upon derepression. Evidence now shows that the two events are not separate but rather are coordinated through composite complexes of repressors and germ cell isoforms of eIF4 factors. Strikingly, the initiation factor isoforms are themselves mRNA selective. The mRNP complexes of translation factors and RBPs are built on specific populations of mRNAs to prime them for subsequent translation initiation. Simple rearrangement of the partners causes a dormant mRNP to become synthetically active in germ cells when and where they are required to support gametogenesis.