Publications

2004
Portereiko MF, Saam J, Mango SE. ZEN-4 / MKLP1 Is Required to Polarize the Foregut Epithelium. 2004;14:932-941.Abstract
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portereiko_2004.pdf
2003
Han Z, Saam JR, Adams HP, Mango SE, Schumacher JM. The C. elegans Tousled-like Kinase (TLK-1) Has an Essential Role in Transcription. Current Biology. 2003;13(22):1921-1929.Abstract
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han2003.pdf
Alder MN, Dames S, Gaudet J, Mango SE. Gene silencing in Caenorhabditis elegans by transitive RNA interference. RNA (New York, N.Y.). 2003;9(1):25-32.Abstract
When a cell is exposed to double-stranded RNA (dsRNA), mRNA from the homologous gene is selectively degraded by a process called RNA interference (RNAi). Here, we provide evidence that dsRNA is amplified in Caenorhabditis elegans to ensure a robust RNAi response. Our data suggest a model in which mRNA targeted by RNAi functions as a template for 5' to 3' synthesis of new dsRNA (termed transitive RNAi). Strikingly, the effect is nonautonomous: dsRNA targeted to a gene expressed in one cell type can lead to transitive RNAi-mediated silencing of a second gene expressed in a distinct cell type. These data suggest dsRNA synthesized in vivo can mediate systemic RNAi.
alder2003.pdf
2002
Jorgensen EM, Mango SE. The art and design of genetic screens: caenorhabditis elegans. Nature reviews. Genetics. 2002;3(5):356-69.Abstract
The nematode Caenorhabditis elegans was chosen as a model genetic organism because its attributes, chiefly its hermaphroditic lifestyle and rapid generation time, make it suitable for the isolation and characterization of genetic mutants. The most important challenge for the geneticist is to design a genetic screen that will identify mutations that specifically disrupt the biological process of interest. Since 1974, when Sydney Brenner published his pioneering genetic screen, researchers have developed increasingly powerful methods for identifying genes and genetic pathways in C. elegans.
jorg_mango2002.pdf
Gaudet J, Mango SE. Regulation of organogenesis by the Caenorhabditis elegans FoxA protein PHA-4. Science (New York, N.Y.). 2002;295(5556):821-5.Abstract
The pha-4 locus encodes a forkhead box A (FoxA/HNF3) transcription factor homolog that specifies organ identity for Caenorhabditis elegans pharyngeal cells. We used microarrays to identify pharyngeal genes and analyzed those genes to determine which were direct PHA-4 targets. Our data suggest that PHA-4 directly activates most or all pharyngeal genes. Furthermore, the relative affinity of PHA-4 for different TRTTKRY (R = A/G, K = T/G, Y = T/C) elements modulates the onset of gene expression, providing a mechanism to activate pharyngeal genes at different developmental stages. We suggest that direct transcriptional regulation of entire gene networks may be a common feature of organ identity genes. View Online
2001
Mango SE. Stop making nonSense: the C. elegans smg genes. Trends in genetics : TIG. 2001;17(11):646-53.Abstract
Cells monitor the quality of their mRNAs and degrade any transcripts that are poorly or incompletely translated. In the nematode Caenorhabditis elegans, degradation by the mRNA surveillance pathway depends on seven smg genes. Three of these genes also have a role in a second mRNA degradation pathway called RNA interference (RNAi), which is triggered by double-stranded RNA (dsRNA). Here I describe what is known about the smg genes and their potential functions in these two mRNA degradation pathways.
mango_tigs2001.pdf
Portereiko MF, Mango SE. Early morphogenesis of the Caenorhabditis elegans pharynx. Developmental biology. 2001;233(2):482-94.Abstract
We investigated the cellular behaviors that accompany the early stages of pharyngeal morphogenesis in Caenorhabditis elegans. The embryonic pharynx develops from a ball of cells into a linear tube connected anteriorly to the buccal cavity and posteriorly to the midgut. By using GFP reporters localized to discrete subcellular regions, we show that pharyngeal morphogenesis can be divided into three stages: (1) lengthening of the nascent pharyngeal lumen by reorientation of apicobasal polarity of anterior pharyngeal cells ("Reorientation"), (2) formation of an epithelium by the buccal cavity cells, which mechanically couples the buccal cavity to the pharynx and anterior epidermis ("Epithelialization"), and (3) a concomitant movement of the pharynx anteriorly and the epidermis of the mouth posteriorly to bring the pharynx, buccal cavity, and mouth into close apposition ("Contraction"). Several models can account for these cellular behaviors, and we distinguish between them by physically or genetically ablating cells within the digestive tract. These studies provide the first description of how the pharynx primordium develops into an epithelial tube, and reveal that pharyngeal morphogenesis resembles aspects of mammalian kidney tubulogenesis.
portereiko01.pdf
2000
Domeier ME, Morse DP, Knight SW, Portereiko M, Bass BL, Mango SE. A link between RNA interference and nonsense-mediated decay in Caenorhabditis elegans. Science (New York, N.Y.). 2000;289(5486):1928-31.Abstract
Double-stranded RNA (dsRNA) inhibits expression of homologous genes by a process involving messenger RNA degradation. To gain insight into the mechanism of degradation, we examined how RNA interference is affected by mutations in the smg genes, which are required for nonsense-mediated decay. For three of six smg genes tested, mutations resulted in animals that were initially silenced by dsRNA but then recovered; wild-type animals remained silenced. The levels of target messenger RNAs were restored during recovery, and RNA editing and degradation of the dsRNA were identical to those of the wild type. We suggest that persistence of RNA interference relies on a subset of smg genes.
domeier2000.pdf
Kaltenbach L, Horner MA, Rothman JH, Mango SE, Barbara S. The TBP-like Factor CeTLF Is Required to Activate RNA Polymerase II Transcription during C . elegans Embryogenesis University of California , Santa Barbara. 2000;6:705-713.Abstract
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kaltenbach2000.pdf
1999
Labouesse M, Mango SE. Patterning the C. elegans embryo: moving beyond the cell lineage. Trends in genetics : TIG [Internet]. 1999;15:307–13. WebsiteAbstract
The Caenorhabditis elegans embryo undergoes a series of stereotyped cell cleavages that generates the organs and tissues necessary for an animal to survive. Here we review two models of embryonic patterning, one that is lineage-based, and one that focuses on domains of organ and tissue precursors. Our evolving view of C. elegans embryogenesis suggests that this animal develops by mechanisms that are qualitatively similar to those used by other animals.
labouesse_mango.pdf
1998
Horner MA, Quintin S, Domeier ME, Kimble J, Labouesse M, Mango SE. pha-4, an HNF-3 homolog, specifies pharyngeal organ identity in Caenorhabditis elegans. 1998:1947-1952.Abstract
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horner98.pdf