Joseph C. Corbo

Bio: Joseph C. Corbo is an academic researcher from Washington University in St. Louis. The author has contributed to research in topics: Enhancer & Transcription factor. The author has an hindex of 38, co-authored 91 publications receiving 7676 citations. Previous affiliations of Joseph C. Corbo include Brigham and Women's Hospital & Stanford University.

Conservation of the sequence and temporal expression of let-7 heterochronic regulatory RNA

Abstract: Two small RNAs regulate the timing of Caenorhabditis elegans development. Transition from the first to the second larval stage fates requires the 22-nucleotide lin-4 RNA and transition from late larval to adult cell fates requires the 21-nucleotide let-7 RNA. The lin-4 and let-7 RNA genes are not homologous to each other, but are each complementary to sequences in the 3' untranslated regions of a set of protein-coding target genes that are normally negatively regulated by the RNAs. Here we have detected let-7 RNAs of ~21 nucleotides in samples from a wide range of animal species, including vertebrate, ascidian, hemichordate, mollusc, annelid and arthropod, but not in RNAs from several cnidarian and poriferan species, Saccharomyces cerevisiae, Escherichia coli or Arabidopsis. We did not detect lin-4 RNA in these species. We found that let-7 temporal regulation is also conserved: let-7 RNA expression is first detected at late larval stages in C. elegans and Drosophila , at 48 hours after fertilization in zebrafish, and in adult stages of annelids and molluscs. The let-7 regulatory RNA may control late temporal transitions during development across animal phylogeny.

Characterization of a notochord-specific enhancer from the Brachyury promoter region of the ascidian, Ciona intestinalis

Abstract: We present evidence that the embryo of the ascidian, Ciona intestinalis, is an easily manipulated system for investigating the establishment of basic chordate tissues and organs. Ciona has a small genome, and simple, well-defined embyronic lineages. Here, we examine the regulatory mechanisms underlying the differentiation of the notochord. Particular efforts center on the regulation of a notochord-specific Ciona Brachyury gene (Ci-Bra). An electroporation method was devised for the efficient incorporation of transgenic DNA into Ciona embryos. This method permitted the identification of a minimal, 434 bp enhancer from the Ci-Bra promoter region that mediates the notochord-restricted expression of both GFP and lacZ reporter genes. This enhancer contains a negative control region that excludes Ci-Bra expression from inappropriate embryonic lineages, including the trunk mesenchyme and tail muscles. Evidence is presented that the enhancer is activated by a regulatory element which is closely related to the recognition sequence of the Suppressor of Hairless transcription factor, thereby raising the possibility that the Notch signaling pathway plays a role in notochord differentiation. We discuss the implications of this analysis with regard to the evolutionary conservation of integrative enhancers, and the subdivision of the axial and paraxial mesoderm in vertebrates.

Doublecortin is required in mice for lamination of the hippocampus but not the neocortex.

Abstract: Doublecortin (DCX) is a microtubule-associated protein that is required for normal neocortical and hippocampal development in humans Mutations in the X-linked human DCX gene cause gross neocortical disorganization (lissencephaly or “smooth brain”) in hemizygous males, whereas heterozygous females show a mosaic phenotype with a normal cortex as well as a second band of misplaced (heterotopic) neurons beneath the cortex (“double cortex syndrome”) We created a mouse carrying a targeted mutation in the Dcx gene Hemizygous male Dcx mice show severe postnatal lethality; the few that survive to adulthood are variably fertile Dcx mutant mice show neocortical lamination that is largely indistinguishable from wild type and show normal patterns of neocortical neurogenesis and neuronal migration In contrast, the hippocampus of both heterozygous females and hemizygous males shows disrupted lamination that is most severe in the CA3 region Behavioral tests show defects in context and cued conditioned fear tests, suggesting that deficits in hippocampal learning accompany the abnormal cytoarchitecture

β-Glucuronidase (GUS) transposons for ecological and genetic studies of rhizobia and other Gram-negative bacteria

Abstract: Summary: A series of transposons are described which contain the gusA gene, encoding β-glucuronidase (GUS), expressed from a variety of promoters, both regulated and constitutive. The regulated promoters include the tac promoter which can be induced by IPTG, and nifH promoters which are symbiotically activated in legume nodules. One transposon contains gusA with a strong Shine-Dalgarno translation initiation context, but no promoter, and thus acts as a promoter-probe transposon. In addition, a gus operon deletion strain of Escherichia coli, and a transposon designed for use in chromosomal mapping using PFGE, are described. The GUS transposons are constructed in a mini-Tn5 system which can be transferred to Gram-negative bacteria by conjugation, and will form stable genomic insertions. Due to the absence of GUS activity in plants and many bacteria of economic importance, these transposons constitute powerful new tools for studying the ecology and population biology of bacteria in the environment and in association with plants, as well as for studies of the fundamental molecular basis of such interactions. The variety of assays available for GUS enable both quantitative assays and spatial localization of marked bacteria to be carried out.

SPAdes, a new genome assembly algorithm and its applications to single-cell sequencing ( 7th Annual SFAF Meeting, 2012)

Abstract: The lion's share of bacteria in various environments cannot be cloned in the laboratory and thus cannot be sequenced using existing technologies. A major goal of single-cell genomics is to complement gene-centric metagenomic data with whole-genome assemblies of uncultivated organisms. Assembly of single-cell data is challenging because of highly non-uniform read coverage as well as elevated levels of sequencing errors and chimeric reads. We describe SPAdes, a new assembler for both single-cell and standard (multicell) assembly, and demonstrate that it improves on the recently released E+V-SC assembler (specialized for single-cell data) and on popular assemblers Velvet and SoapDeNovo (for multicell data). SPAdes generates single-cell assemblies, providing information about genomes of uncultivatable bacteria that vastly exceeds what may be obtained via traditional metagenomics studies. SPAdes is available online ( http://bioinf.spbau.ru/spades ). It is distributed as open source software.

MicroRNAs: small RNAs with a big role in gene regulation

Abstract: MicroRNAs are a family of small, non-coding RNAs that regulate gene expression in a sequence-specific manner. The two founding members of the microRNA family were originally identified in Caenorhabditis elegans as genes that were required for the timed regulation of developmental events. Since then, hundreds of microRNAs have been identified in almost all metazoan genomes, including worms, flies, plants and mammals. MicroRNAs have diverse expression patterns and might regulate various developmental and physiological processes. Their discovery adds a new dimension to our understanding of complex gene regulatory networks.

Oncomirs : microRNAs with a role in cancer

Abstract: I MicroRNAs (miRNAs) are an abundant class of small non-protein-coding RNAs that function as negative gene regulators. They regulate diverse biological processes, and bioinformatic data indicates that each miRNA can control hundreds of gene targets, underscoring the potential influence of miRNAs on almost every genetic pathway. Recent evidence has shown that miRNA mutations or mis-expression correlate with various human cancers and indicates that miRNAs can function as tumour suppressors and oncogenes. miRNAs have been shown to repress the expression of important cancer-related genes and might prove useful in the diagnosis and treatment of cancer.