TY - JOUR T1 - Genetic characterization of smg-8 mutants reveals no role in C. elegans nonsense mediated decay JF - PLoS One Y1 - 2012 A1 - Rosains, Jacqueline A1 - Mango, Susan E AB - The nonsense mediated decay (NMD) pathway degrades mRNAs bearing premature translation termination codons. In mammals, SMG-8 has been implicated in the NMD pathway, in part by its association with SMG-1 kinase. Here we use four independent assays to show that C. elegans smg-8 is not required to degrade nonsense-containing mRNAs. We examine the genetic requirement for smg-8 to destabilize the endogenous, natural NMD targets produced by alternative splicing of rpl-7a and rpl-12. We test smg-8 for degradation of the endogenous, NMD target generated by unc-54(r293), which lacks a normal polyadenylation site. We probe the effect of smg-8 on the exogenous NMD target produced by myo-3::GFP, which carries a long 3′ untranslated region that destabilizes mRNAs. None of these known NMD targets is influenced by smg-8 mutations. In addition, smg-8 animals lack classical Smg mutant phenotypes such as a reduced brood size or abnormal vulva. We conclude that smg-8 is unlikely to encode a component critical for NMD. VL - 7 IS - 11 ER - TY - JOUR T1 - Ageing: generations of longevity JF - Nature Y1 - 2011 A1 - Mango, Susan E VL - 479 IS - 7373 ER - TY - JOUR T1 - Locking the genome: nuclear organization and cell fate. JF - Current opinion in genetics & development Y1 - 2011 A1 - Meister, Peter A1 - Mango, Susan E A1 - Gasser, Susan M AB -
The differentiation of pluripotent or totipotent cells into various differentiated cell types is accompanied by a restriction of gene expression patterns, alteration in histone and DNA methylation, and changes in the gross nuclear organization of eu- and heterochromatic domains. Several recent studies have coupled genome-wide mapping of histone modifications with changes in gene expression. Other studies have examined changes in the subnuclear positioning of tissue-specific genes upon transcriptional induction or repression. Here we summarize intriguing correlations of the three phenomena, which suggest that in some cases causal relationships may exist.
View OnlineVL - 21 ER - TY - ABST T1 - Dynamic chromatin organization during foregut development mediated by the organ selector gene PHA-4/FoxA. Y1 - 2010 A1 - Fakhouri, Tala H I A1 - Stevenson, Jeff A1 - Chisholm, Andrew D A1 - Mango, Susan E AB -
Central regulators of cell fate, or selector genes, establish the identity of cells by direct regulation of large cohorts of genes. In Caenorhabditis elegans, foregut (or pharynx) identity relies on the FoxA transcription factor PHA-4, which activates different sets of target genes at various times and in diverse cellular environments. An outstanding question is how PHA-4 distinguishes between target genes for appropriate transcriptional control. We have used the Nuclear Spot Assay and GFP reporters to examine PHA-4 interactions with target promoters in living embryos and with single cell resolution. While PHA-4 was found throughout the digestive tract, binding and activation of pharyngeally expressed promoters was restricted to a subset of pharyngeal cells and excluded from the intestine. An RNAi screen of candidate nuclear factors identified emerin (emr-1) as a negative regulator of PHA-4 binding within the pharynx, but emr-1 did not modulate PHA-4 binding in the intestine. Upon promoter association, PHA-4 induced large-scale chromatin de-compaction, which, we hypothesize, may facilitate promoter access and productive transcription. Our results reveal two tiers of PHA-4 regulation. PHA-4 binding is prohibited in intestinal cells, preventing target gene expression in that organ. PHA-4 binding within the pharynx is limited by the nuclear lamina component EMR-1/emerin. The data suggest that association of PHA-4 with its targets is a regulated step that contributes to promoter selectivity during organ formation. We speculate that global re-organization of chromatin architecture upon PHA-4 binding promotes competence of pharyngeal gene transcription and, by extension, foregut development.
View OnlineJF - PLoS genetics VL - 6 IS - 8 N1 -
n/aER - TY - ABST T1 - Genome-wide identification of binding sites defines distinct functions for Caenorhabditis elegans PHA-4/FOXA in development and environmental response. Y1 - 2010 A1 - Zhong, Mei A1 - Niu, Wei A1 - Lu, Zhi John A1 - Sarov, Mihail A1 - Murray, John I A1 - Janette, Judith A1 - Raha, Debasish A1 - Sheaffer, Karyn L A1 - Lam, Hugo Y K A1 - Preston, Elicia A1 - Slightham, Cindie A1 - Hillier, LaDeana W A1 - Brock, Trisha A1 - Agarwal, Ashish A1 - Auerbach, Raymond A1 - Hyman, Anthony a A1 - Gerstein, Mark A1 - Mango, Susan E A1 - Kim, Stuart K A1 - Waterston, Robert H A1 - Reinke, Valerie A1 - Snyder, Michael AB -
Transcription factors are key components of regulatory networks that control development, as well as the response to environmental stimuli. We have established an experimental pipeline in Caenorhabditis elegans that permits global identification of the binding sites for transcription factors using chromatin immunoprecipitation and deep sequencing. We describe and validate this strategy, and apply it to the transcription factor PHA-4, which plays critical roles in organ development and other cellular processes. We identified thousands of binding sites for PHA-4 during formation of the embryonic pharynx, and also found a role for this factor during the starvation response. Many binding sites were found to shift dramatically between embryos and starved larvae, from developmentally regulated genes to genes involved in metabolism. These results indicate distinct roles for this regulator in two different biological processes and demonstrate the versatility of transcription factors in mediating diverse biological roles.
View OnlineJF - PLoS genetics VL - 6 IS - 2 N1 -
n/aER - TY - ABST T1 - Q & A: Susan Mango Y1 - 2009 A1 - Mango, Susan AB -
View OnlineJF - Current Biology VL - 19 IS - 7 ER - TY - ABST T1 - The molecular basis of organ formation: insights from the C. elegans foregut. Y1 - 2009 A1 - Mango, Susan E AB -
The digestive tracts of many animals are epithelial tubes with specialized compartments to break down food, remove wastes, combat infection, and signal nutrient availability. C. elegans possesses a linear, epithelial gut tube with foregut, midgut, and hindgut sections. The simple anatomy belies the developmental complexity that is involved in forming the gut from a pool of heterogeneous precursor cells. Here, I focus on the processes that specify cell fates and control morphogenesis within the embryonic foregut (pharynx) and the developmental roles of the pharynx after birth. Maternally donated factors in the pregastrula embryo converge on pha-4, a FoxA transcription factor that specifies organ identity for pharyngeal precursors. Positive feedback loops between PHA-4 and other transcription factors ensure commitment to pharyngeal fate. Binding-site affinity of PHA-4 for its target promoters contributes to the progression of the pharyngeal precursors towards differentiation. During morphogenesis, the pharyngeal precursors form an epithelial tube in a process that is independent of cadherins, catenins, and integrins but requires the kinesin zen-4/MKLP1. After birth, the pharynx and/or pha-4 are involved in repelling pathogens and controlling aging.
View OnlineJF - Annual review of cell and developmental biology VL - 25 UR - http://arjournals.annualreviews.org/doi/abs/10.1146/annurev.cellbio.24.110707.175411?url_ver=Z39.88-2003&rfr_id=ori:rid:crossref.org&rfr_dat=cr_pub%3dncbi.nlm.nih.gov N1 -
n/aER - TY - ABST T1 - The polycomb complex protein mes-2/E(z) promotes the transition from developmental plasticity to differentiation in C. elegans embryos. Y1 - 2009 A1 - Yuzyuk, T A1 - Fakhouri, T H I A1 - Kiefer, J A1 - Mango, S E AB -
We have used expression profiling and in vivo imaging to characterize Caenorhabditis elegans embryos as they transit from a developmentally plastic state to the onset of differentiation. Normally, this transition is accompanied by activation of developmental regulators and differentiation genes, downregulation of early-expressed genes, and large-scale reorganization of chromatin. We find that loss of plasticity and differentiation onset depends on the Polycomb complex protein mes-2/E(Z). mes-2 mutants display prolonged developmental plasticity in response to heterologous developmental regulators. Early-expressed genes remain active, differentiation genes fail to reach wild-type levels, and chromatin retains a decompacted morphology in mes-2 mutants. By contrast, loss of the developmental regulators pha-4/FoxA or end-1/GATA does not prolong plasticity. This study establishes a model by which to analyze developmental plasticity within an intact embryo. mes-2 orchestrates large-scale changes in chromatin organization and gene expression to promote the timely loss of developmental plasticity. Our findings indicate that loss of plasticity can be uncoupled from cell fate specification.
View OnlineJF - Developmental cell PB - Elsevier Ltd VL - 16 IS - 5 N1 -
n/aER - TY - ABST T1 - The Target of Rapamycin pathway antagonizes pha-4/FoxA to control development and aging. Y1 - 2008 A1 - Sheaffer, Karyn L A1 - Updike, Dustin L A1 - Mango, Susan E AB -
FoxA factors are critical regulators of embryonic development and postembryonic life, but little is know about the upstream pathways that modulate their activity. C. elegans pha-4 encodes a FoxA transcription factor that is required to establish the foregut in embryos and to control growth and longevity after birth. We previously identified the AAA+ ATPase homolog ruvb-1 as a potent suppressor of pha-4 mutations.
View OnlineJF - Current biology : CB VL - 18 IS - 18 ER - TY - ABST T1 - Wormnet: a crystal ball for Caenorhabditis elegans Y1 - 2008 A1 - Von Stetina, Stephen E A1 - Mango, Susan E AB -
An integrated gene network for Caenorhabditis elegans using data from multiple genome-wide screens encompasses most protein-coding genes and can accurately predict their phenotypes.
View OnlineJF - Genome biology VL - 9 IS - 6 ER - TY - ABST T1 - PHA-4/FoxA cooperates with TAM-1/TRIM to regulate cell fate restriction in the C. elegans foregut. Y1 - 2007 A1 - Kiefer, Julie C A1 - Smith, Pliny a A1 - Mango, Susan E AB -
A key question in development is how pluripotent progenitors are progressively restricted to acquire specific cell fates. Here we investigate how embryonic blastomeres in C. elegans develop into foregut (pharynx) cells in response to the selector gene PHA-4/FoxA. When pha-4 is removed from pharyngeal precursors, they exhibit two alternative responses. Before late-gastrulation (8E stage), these cells lose their pharyngeal identity and acquire an alternative fate such as ectoderm (Specification stage). After the Specification stage, mutant cells develop into aberrant pharyngeal cells (Morphogenesis/Differentiation stage). Two lines of evidence suggest that the Specification stage depends on transcriptional repression of ectodermal genes by pha-4. First, pha-4 exhibits strong synthetic phenotypes with the B class synMuv gene tam-1 (Tandam Array expression Modifier 1) and with a mediator of transcriptional repression, the NuRD complex (NUcleosome Remodeling and histone Deacetylase). Second, pha-4 associates with the promoter of the ectodermal regulator lin-26 and is required to repress lin-26 expression. We propose that restriction of early blastomeres to the pharyngeal fate depends on both repression of ectodermal genes and activation of pharyngeal genes by PHA-4.JF - Developmental biology VL - 303 IS - 2 N1 -
n/aER - TY - ABST T1 - The C. elegans pharynx: a model for organogenesis. Y1 - 2007 A1 - Mango, Susan E AB -
The C. elegans foregut (pharynx) has emerged as a powerful system to study organ formation during embryogenesis. Here I review recent advances regarding cell-fate specification and epithelial morphogenesis during pharynx development. Maternally-supplied gene products function prior to gastrulation to establish pluripotent blastomeres. As gastrulation gets under way, pharyngeal precursors become committed to pharyngeal fate in a process that requires PHA-4/FoxA and the Tbox transcription factors TBX-2, TBX-35, TBX-37 and TBX-38. Subsequent waves of gene expression depend on the affinity of PHA-4 for its target promoters, coupled with combinatorial strategies such as feed-forward and positive-feedback loops. During later embryogenesis, pharyngeal precursors undergo reorganization and a mesenchymal-to-epithelial transition to form the linear gut tube. Surprisingly, epithelium formation does not depend on cadherins, catenins or integrins. Rather, the kinesin ZEN-4/MKLP1 and CYK-4/RhoGAP are critical to establish the apical domain during epithelial polarization. Finally, I discuss similarities and differences between the nematode pharynx and the vertebrate heart.JF - WormBook : the online review of C. elegans biology UR - http://www.wormbook.org/chapters/www_organformation/organformation.html N1 -
n/aER - TY - ABST T1 - Role of T-box gene tbx-2 for anterior foregut muscle development in C. elegans. Y1 - 2007 A1 - Smith, Pliny A1 - Mango, Susan E AB -
During organogenesis, pluripotent precursor cells acquire a defined identity such as muscle or nerve. The transition from naïve precursor towards the differentiated state is characterized by sequential waves of gene expression that are determined by regulatory transcription factors. A key question is how transcriptional circuitry dictates the succession of events that accompanies developmental competence, cell fate specification and differentiation. To address this question, we have examined how anterior muscles are established within the Caenorhabditis elegans foregut (pharynx). We find that the T-box transcription factor tbx-2 is essential to form anterior pharyngeal muscles from the ABa blastomere. In the absence of tbx-2 function, ABa-derived cells initiate development normally: they receive glp-1/Notch signaling cues, activate the T-box gene TBX-38 and express the organ selector gene PHA-4/FoxA. However, these cells subsequently arrest development, extinguish PHA-4 and fail to activate PHA-4 target genes. tbx-2 mutant cells do not undergo apoptosis and there is no evidence for adoption of an alternative fate. TBX-2 is expressed in ABa descendants and depends on activation by pha-4 and repression by components of glp-1/Notch signaling. Our analysis suggests that a positive feedback loop between tbx-2 and pha-4 is required for ABa-derived precursors to commit to pharyngeal muscle fate.JF - Developmental biology VL - 302 IS - 1 N1 -
n/aER - TY - ABST T1 - A gene-centered C. elegans protein-DNA interaction network. Y1 - 2006 A1 - Deplancke, Bart A1 - Mukhopadhyay, Arnab A1 - Ao, Wanyuan A1 - Elewa, Ahmed M A1 - Grove, Christian a A1 - Martinez, Natalia J A1 - Sequerra, Reynaldo A1 - Doucette-Stamm, Lynn A1 - Reece-Hoyes, John S A1 - Hope, Ian a A1 - Tissenbaum, Heidi a A1 - Mango, Susan E A1 - Walhout, Albertha J M AB -
Transcription regulatory networks consist of physical and functional interactions between transcription factors (TFs) and their target genes. The systematic mapping of TF-target gene interactions has been pioneered in unicellular systems, using "TF-centered" methods (e.g., chromatin immunoprecipitation). However, metazoan systems are less amenable to such methods. Here, we used "gene-centered" high-throughput yeast one-hybrid (Y1H) assays to identify 283 interactions between 72 C. elegans digestive tract gene promoters and 117 proteins. The resulting protein-DNA interaction (PDI) network is highly connected and enriched for TFs that are expressed in the digestive tract. We provide functional annotations for approximately 10% of all worm TFs, many of which were previously uncharacterized, and find ten novel putative TFs, illustrating the power of a gene-centered approach. We provide additional in vivo evidence for multiple PDIs and illustrate how the PDI network provides insights into metazoan differential gene expression at a systems level.JF - Cell VL - 125 IS - 6 N1 -
n/aER - TY - ABST T1 - Temporal regulation of foregut development by HTZ-1/H2A.Z and PHA-4/FoxA. Y1 - 2006 A1 - Updike, Dustin L A1 - Mango, Susan E AB -
The histone variant H2A.Z is evolutionarily conserved and plays an essential role in mice, Drosophila, and Tetrahymena. The essential function of H2A.Z is unknown, with some studies suggesting a role in transcriptional repression and others in activation. Here we show that Caenorhabditis elegans HTZ-1/H2A.Z and the remodeling complex MYS-1/ESA1-SSL-1/SWR1 synergize with the FoxA transcription factor PHA-4 to coordinate temporal gene expression during foregut development. We observe dramatic genetic interactions between pha-4 and htz-1, mys-1, and ssl-1. A survey of transcription factors reveals that this interaction is specific, and thus pha-4 is acutely sensitive to reductions in these three proteins. Using a nuclear spot assay to visualize HTZ-1 in living embryos as organogenesis proceeds, we show that HTZ-1 is recruited to foregut promoters at the time of transcriptional onset, and this recruitment requires PHA-4. Loss of htz-1 by RNAi is lethal and leads to delayed expression of a subset of foregut genes. Thus, the effects of PHA-4 on temporal regulation can be explained in part by recruitment of HTZ-1 to target promoters. We suggest PHA-4 and HTZ-1 coordinate temporal gene expression by modulating the chromatin environment.JF - PLoS genetics VL - 2 IS - 9 N1 -
n/aER - TY - ABST T1 - CYK-4/GAP provides a localized cue to initiate anteroposterior polarity upon fertilization. Y1 - 2006 A1 - Jenkins, Noah A1 - Saam, Jennifer R. A1 - Mango, Susan E AB -
The Caenorhabditis elegans anteroposterior axis is established in response to fertilization by sperm. Here we present evidence that RhoA, the guanine nucleotide-exchange factor ECT-2, and the Rho guanosine triphosphatase-activating protein CYK-4 modulate myosin light-chain activity to create a gradient of actomyosin, which establishes the anterior domain. CYK-4 is enriched within sperm, and paternally donated CYK-4 is required for polarity. These data suggest that CYK-4 provides a molecular link between fertilization and polarity establishment in the one-cell embryo. Orthologs of CYK-4 are expressed in sperm of other species, which suggests that this cue may be evolutionarily conserved.
View OnlineJF - Science (New York, N.Y.) VL - 313 IS - 5791 ER - TY - ABST T1 - Esearch rticles Y1 - 2004 A1 - Ao, Wanyuan A1 - Gaudet, Jeb A1 - Kent, W James A1 - Muttumu, Srikanth A1 - Mango, Susan E AB -
n/aVL - 305 IS - September N1 -
n/aER - TY - ABST T1 - The coordinate regulation of pharyngeal development in C. elegans by lin-35/Rb, pha-1, and ubc-18. Y1 - 2004 A1 - Fay, David S A1 - Qiu, Xiaohui A1 - Large, Edward A1 - Smith, Christopher P A1 - Mango, Susan A1 - Johanson, Bethany L AB -
Organ development is a complex process involving the coordination of cell proliferation, differentiation, and morphogenetic events. Using a screen to identify genes that function coordinately with lin-35/Rb during animal development, we have isolated a weak loss-of-function (LOF) mutation in pha-1. lin-35; pha-1 double mutants are defective at an early step in pharyngeal morphogenesis leading to an abnormal pharyngeal architecture. pha-1 is also synthetically lethal with other class B synthetic multivulval (SynMuv) genes including the C. elegans E2F homolog, efl-1. Reporter analyses indicate that pha-1 is broadly expressed during embryonic development and that its functions reside in the cytoplasm. We also provide genetic and phenotypic evidence to support the model that PHA-1, a novel protein, and UBC-18, a ubiquitin-conjugating enzyme that we have previously shown to function with lin-35 during pharyngeal development, act in parallel pathways to regulate the activity of a common cellular target.JF - Developmental biology VL - 271 IS - 1 N1 -
n/aER - TY - ABST T1 - Whole-genome analysis of temporal gene expression during foregut development. Y1 - 2004 A1 - Gaudet, Jeb A1 - Muttumu, Srikanth A1 - Horner, Michael A1 - Mango, Susan E AB -
We have investigated the cis-regulatory network that mediates temporal gene expression during organogenesis. Previous studies demonstrated that the organ selector gene pha-4/FoxA is critical to establish the onset of transcription of Caenorhabditis elegans foregut (pharynx) genes. Here, we discover additional cis-regulatory elements that function in combination with PHA-4. We use a computational approach to identify candidate cis-regulatory sites for genes activated either early or late during pharyngeal development. Analysis of natural or synthetic promoters reveals that six of these sites function in vivo. The newly discovered temporal elements, together with predicted PHA-4 sites, account for the onset of expression of roughly half of the pharyngeal genes examined. Moreover, combinations of temporal elements and PHA-4 sites can be used in genome-wide searches to predict pharyngeal genes, with more than 85% accuracy for their onset of expression. These findings suggest a regulatory code for temporal gene expression during foregut development and provide a means to predict gene expression patterns based solely on genomic sequence.JF - PLoS biology VL - 2 IS - 11 N1 -
n/aER - TY - ABST T1 - A map of the interactome network of the metazoan C. elegans. Y1 - 2004 A1 - Li, Siming A1 - Armstrong, Christopher M A1 - Bertin, Nicolas A1 - Ge, Hui A1 - Milstein, Stuart A1 - Boxem, Mike A1 - Vidalain, Pierre-Olivier A1 - Han, Jing-Dong J A1 - Chesneau, Alban A1 - Hao, Tong A1 - Goldberg, Debra S A1 - Li, Ning A1 - Martinez, Monica A1 - Rual, Jean-François A1 - Lamesch, Philippe A1 - Xu, Lai A1 - Tewari, Muneesh A1 - Wong, Sharyl L A1 - Zhang, Lan V A1 - Berriz, Gabriel F A1 - Jacotot, Laurent A1 - Vaglio, Philippe A1 - Reboul, Jérôme A1 - Hirozane-Kishikawa, Tomoko A1 - Li, Qianru A1 - Gabel, Harrison W A1 - Elewa, Ahmed A1 - Baumgartner, Bridget A1 - Rose, Debra J A1 - Yu, Haiyuan A1 - Bosak, Stephanie A1 - Sequerra, Reynaldo A1 - Fraser, Andrew A1 - Mango, Susan E A1 - Saxton, William M A1 - Strome, Susan A1 - Van Den Heuvel, Sander A1 - Piano, Fabio A1 - Vandenhaute, Jean A1 - Sardet, Claude A1 - Gerstein, Mark A1 - Doucette-Stamm, Lynn A1 - Gunsalus, Kristin C A1 - Harper, J Wade A1 - Cusick, Michael E A1 - Roth, Frederick P A1 - Hill, David E A1 - Vidal, Marc AB -
To initiate studies on how protein-protein interaction (or "interactome") networks relate to multicellular functions, we have mapped a large fraction of the Caenorhabditis elegans interactome network. Starting with a subset of metazoan-specific proteins, more than 4000 interactions were identified from high-throughput, yeast two-hybrid (HT=Y2H) screens. Independent coaffinity purification assays experimentally validated the overall quality of this Y2H data set. Together with already described Y2H interactions and interologs predicted in silico, the current version of the Worm Interactome (WI5) map contains approximately 5500 interactions. Topological and biological features of this interactome network, as well as its integration with phenome and transcriptome data sets, lead to numerous biological hypotheses.JF - Science (New York, N.Y.) VL - 303 IS - 5657 N1 -
n/aER - TY - ABST T1 - ZEN-4 / MKLP1 Is Required to Polarize the Foregut Epithelium Y1 - 2004 A1 - Portereiko, Michael F A1 - Saam, Jennifer A1 - Mango, Susan E AB -
n/aVL - 14 N1 -
n/aER - TY - ABST T1 - The C. elegans Tousled-like Kinase (TLK-1) Has an Essential Role in Transcription Y1 - 2003 A1 - Han, Zhenbo A1 - Saam, Jennifer R. A1 - Adams, Henry P. A1 - Mango, Susan E A1 - Schumacher, Jill M. AB -
n/aJF - Current Biology VL - 13 IS - 22 N1 -
n/aER - TY - ABST T1 - Gene silencing in Caenorhabditis elegans by transitive RNA interference. Y1 - 2003 A1 - Alder, Matthew N A1 - Dames, Shale A1 - Gaudet, Jeffrey A1 - Mango, Susan E AB -
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.JF - RNA (New York, N.Y.) VL - 9 IS - 1 N1 -
n/aER - TY - ABST T1 - The art and design of genetic screens: caenorhabditis elegans. Y1 - 2002 A1 - Jorgensen, Erik M A1 - Mango, Susan E AB -
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.JF - Nature reviews. Genetics VL - 3 IS - 5 N1 -
n/aER - TY - ABST T1 - Regulation of organogenesis by the Caenorhabditis elegans FoxA protein PHA-4. Y1 - 2002 A1 - Gaudet, J A1 - Mango, S E AB -
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 OnlineJF - Science (New York, N.Y.) VL - 295 IS - 5556 ER - TY - ABST T1 - Stop making nonSense: the C. elegans smg genes. Y1 - 2001 A1 - Mango, S E AB -
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.JF - Trends in genetics : TIG VL - 17 IS - 11 N1 -
n/aER - TY - ABST T1 - Early morphogenesis of the Caenorhabditis elegans pharynx. Y1 - 2001 A1 - Portereiko, M F A1 - Mango, S E AB -
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.JF - Developmental biology VL - 233 IS - 2 N1 -
n/aER - TY - ABST T1 - A link between RNA interference and nonsense-mediated decay in Caenorhabditis elegans. Y1 - 2000 A1 - Domeier, M E A1 - Morse, D P A1 - Knight, S W A1 - Portereiko, M A1 - Bass, B L A1 - Mango, S E AB -
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.JF - Science (New York, N.Y.) VL - 289 IS - 5486 ER - TY - ABST T1 - The TBP-like Factor CeTLF Is Required to Activate RNA Polymerase II Transcription during C . elegans Embryogenesis University of California , Santa Barbara Y1 - 2000 A1 - Kaltenbach, Linda A1 - Horner, Michael A A1 - Rothman, Joel H A1 - Mango, Susan E A1 - Barbara, Santa AB -
n/aVL - 6 N1 -
n/aER - TY - JOUR T1 - Patterning the C. elegans embryo: moving beyond the cell lineage. JF - Trends in genetics : TIG Y1 - 1999 A1 - Labouesse, M A1 - Mango, S E AB -
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.VL - 15 UR - http://www.ncbi.nlm.nih.gov/pubmed/10431192 N1 -
n/aER - TY - ABST T1 - pha-4, an HNF-3 homolog, specifies pharyngeal organ identity in Caenorhabditis elegans Y1 - 1998 A1 - Horner, Michael A A1 - Quintin, Sophie A1 - Domeier, Mary Ellen A1 - Kimble, Judith A1 - Labouesse, Michel A1 - Mango, Susan E AB -