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Rna Recognition By The Caenorhabditis Elegans Oocyte Maturation Determinant Oma-1, Ebru Kaymak, Sean Ryder Oct 2015

Rna Recognition By The Caenorhabditis Elegans Oocyte Maturation Determinant Oma-1, Ebru Kaymak, Sean Ryder

Sean P. Ryder

Maternally supplied mRNAs encode proteins that pattern early embryos in many species. In the nematode Caenorhabditis elegans, a suite of RNA-binding proteins regulates expression of maternal mRNAs during oogenesis, the oocyte to embryo transition, and early embryogenesis. To understand how these RNA-binding proteins contribute to development, it is necessary to determine how they select specific mRNA targets for regulation. OMA-1 and OMA-2 are redundant proteins required for oocyte maturation--an essential part of meiosis that prepares oocytes for fertilization. Both proteins have CCCH type tandem zinc finger RNA-binding domains. Here, we define the RNA binding specificity of OMA-1 and demonstrate that …


The Decapping Scavenger Enzyme Dcs-1 Controls Microrna Levels In Caenorhabditis Elegans, Gabriel Bosse, Stefan Ruegger, Maria Ow, Alejandro Vasquez-Rifo, Evelyne Rondeau, Victor Ambros, Helge Grosshans, Martin Simard Oct 2015

The Decapping Scavenger Enzyme Dcs-1 Controls Microrna Levels In Caenorhabditis Elegans, Gabriel Bosse, Stefan Ruegger, Maria Ow, Alejandro Vasquez-Rifo, Evelyne Rondeau, Victor Ambros, Helge Grosshans, Martin Simard

Victor R. Ambros

In metazoans, microRNAs play a critical role in the posttranscriptional regulation of genes required for cell proliferation and differentiation. MicroRNAs themselves are regulated by a multitude of mechanisms influencing their transcription and posttranscriptional maturation. However, there is only sparse knowledge on pathways regulating the mature, functional form of microRNA. Here, we uncover the implication of the decapping scavenger protein DCS-1 in the control of microRNA turnover. In Caenorhabditis elegans, mutations in dcs-1 increase the levels of functional microRNAs. We demonstrate that DCS-1 interacts with the exonuclease XRN-1 to promote microRNA degradation in an independent manner from its known decapping scavenger …


Developmental Decline In Neuronal Regeneration By The Progressive Change Of Two Intrinsic Timers, Yan Zou, Hui Chiu, Anna Zinovyeva, Victor Ambros, Chiou-Fen Chuang, Chieh Chang Oct 2015

Developmental Decline In Neuronal Regeneration By The Progressive Change Of Two Intrinsic Timers, Yan Zou, Hui Chiu, Anna Zinovyeva, Victor Ambros, Chiou-Fen Chuang, Chieh Chang

Victor R. Ambros

Like mammalian neurons, Caenorhabditis elegans neurons lose axon regeneration ability as they age, but it is not known why. Here, we report that let-7 contributes to a developmental decline in anterior ventral microtubule (AVM) axon regeneration. In older AVM axons, let-7 inhibits regeneration by down-regulating LIN-41, an important AVM axon regeneration-promoting factor. Whereas let-7 inhibits lin-41 expression in older neurons through the lin-41 3' untranslated region, lin-41 inhibits let-7 expression in younger neurons through Argonaute ALG-1. This reciprocal inhibition ensures that axon regeneration is inhibited only in older neurons. These findings show that a let-7-lin-41 regulatory circuit, which was previously …


The Developmental Timing Regulator Hbl-1 Modulates The Dauer Formation Decision In Caenorhabditis Elegans, Xantha Karp, Victor Ambros Oct 2015

The Developmental Timing Regulator Hbl-1 Modulates The Dauer Formation Decision In Caenorhabditis Elegans, Xantha Karp, Victor Ambros

Victor R. Ambros

Animals developing in the wild encounter a range of environmental conditions, and so developmental mechanisms have evolved that can accommodate different environmental contingencies. Harsh environmental conditions cause Caenorhabditis elegans larvae to arrest as stress-resistant "dauer" larvae after the second larval stage (L2), thereby indefinitely postponing L3 cell fates. HBL-1 is a key transcriptional regulator of L2 vs. L3 cell fate. Through the analysis of genetic interactions between mutations of hbl-1 and of genes encoding regulators of dauer larva formation, we find that hbl-1 can also modulate the dauer formation decision in a complex manner. We propose that dynamic interactions between …


Micrornas And Developmental Timing, Victor Ambros Oct 2015

Micrornas And Developmental Timing, Victor Ambros

Victor R. Ambros

MicroRNAs regulate temporal transitions in gene expression associated with cell fate progression and differentiation throughout animal development. Genetic analysis of developmental timing in the nematode Caenorhabditis elegans identified two evolutionarily conserved microRNAs, lin-4/mir-125 and let-7, that regulate cell fate progression and differentiation in C. elegans cell lineages. MicroRNAs perform analogous developmental timing functions in other animals, including mammals. By regulating cell fate choices and transitions between pluripotency and differentiation, microRNAs help to orchestrate developmental events throughout the developing animal, and to play tissue homeostasis roles important for disease, including cancer.


Dauer Larva Quiescence Alters The Circuitry Of Microrna Pathways Regulating Cell Fate Progression In C. Elegans, Xantha Karp, Victor Ambros Oct 2015

Dauer Larva Quiescence Alters The Circuitry Of Microrna Pathways Regulating Cell Fate Progression In C. Elegans, Xantha Karp, Victor Ambros

Victor R. Ambros

In C. elegans larvae, the execution of stage-specific developmental events is controlled by heterochronic genes, which include those encoding a set of transcription factors and the microRNAs that regulate the timing of their expression. Under adverse environmental conditions, developing larvae enter a stress-resistant, quiescent stage called 'dauer'. Dauer larvae are characterized by the arrest of all progenitor cell lineages at a stage equivalent to the end of the second larval stage (L2). If dauer larvae encounter conditions favorable for resumption of reproductive growth, they recover and complete development normally, indicating that post-dauer larvae possess mechanisms to accommodate an indefinite period …


Nhl-2 Modulates Microrna Activity In Caenorhabditis Elegans, Christopher Hammell, Isabella Lubin, Peter Boag, T. Keith Blackwell, Victor Ambros Oct 2015

Nhl-2 Modulates Microrna Activity In Caenorhabditis Elegans, Christopher Hammell, Isabella Lubin, Peter Boag, T. Keith Blackwell, Victor Ambros

Victor R. Ambros

TRIM-NHL proteins represent a large class of metazoan proteins implicated in development and disease. We demonstrate that a C. elegans TRIM-NHL protein, NHL-2, functions as a cofactor for the microRNA-induced silencing complex (miRISC) and thereby enhances the posttranscriptional repression of several genetically verified microRNA targets, including hbl-1 and let-60/Ras (by the let-7 family of microRNAs) and cog-1 (by the lsy-6 microRNA). NHL-2 is localized to cytoplasmic P-bodies and physically associates with the P-body protein CGH-1 and the core miRISC components ALG-1/2 and AIN-1. nhl-2 and cgh-1 mutations compromise the repression of microRNA targets in vivo but do not affect microRNA …


Mirwip: Microrna Target Prediction Based On Microrna-Containing Ribonucleoprotein-Enriched Transcripts, Molly Hammell, Dang Long, Liang Zhang, Andrew Lee, C. Steven Carmack, Min Han, Ye Ding, Victor Ambros Oct 2015

Mirwip: Microrna Target Prediction Based On Microrna-Containing Ribonucleoprotein-Enriched Transcripts, Molly Hammell, Dang Long, Liang Zhang, Andrew Lee, C. Steven Carmack, Min Han, Ye Ding, Victor Ambros

Victor R. Ambros

Target prediction for animal microRNAs (miRNAs) has been hindered by the small number of verified targets available to evaluate the accuracy of predicted miRNA-target interactions. Recently, a dataset of 3,404 miRNA-associated mRNA transcripts was identified by immunoprecipitation of the RNA-induced silencing complex components AIN-1 and AIN-2. Our analysis of this AIN-IP dataset revealed enrichment for defining characteristics of functional miRNA-target interactions, including structural accessibility of target sequences, total free energy of miRNA-target hybridization and topology of base-pairing to the 5' seed region of the miRNA. We used these enriched characteristics as the basis for a quantitative miRNA target prediction method, …


Micrornas: Genetically Sensitized Worms Reveal New Secrets, Victor Ambros Oct 2015

Micrornas: Genetically Sensitized Worms Reveal New Secrets, Victor Ambros

Victor R. Ambros

Why do many microRNA gene mutants display no evident phenotype? Multiply mutant worms that are selectively impaired in genetic regulatory network activities have been used to uncover previously unknown functions for numerous Caenorhabditis elegans microRNAs.


Prb/Cki Pathways At The Interface Of Cell Cycle And Development, Victor Ambros Oct 2015

Prb/Cki Pathways At The Interface Of Cell Cycle And Development, Victor Ambros

Victor R. Ambros

Comment on: The cyclin-dependent kinase inhibitors, cki-1 and cki-2, act in overlapping but distinct pathways to control cell-cycle quiescence during C. elegans development. Buck SH, et al. Cell Cycle 2009; 8:2613-20.


A Compendium Of Caenorhabditis Elegans Rna Binding Proteins Predicts Extensive Regulation At Multiple Levels, Alex Tamburino, Sean Ryder, Albertha Walhout May 2015

A Compendium Of Caenorhabditis Elegans Rna Binding Proteins Predicts Extensive Regulation At Multiple Levels, Alex Tamburino, Sean Ryder, Albertha Walhout

Sean P. Ryder

Gene expression is regulated at multiple levels, including transcription and translation, as well as mRNA and protein stability. Although systems-level functions of transcription factors and microRNAs are rapidly being characterized, few studies have focused on the posttranscriptional gene regulation by RNA binding proteins (RBPs). RBPs are important to many aspects of gene regulation. Thus, it is essential to know which genes encode RBPs, which RBPs regulate which gene(s), and how RBP genes are themselves regulated. Here we provide a comprehensive compendium of RBPs from the nematode Caenorhabditis elegans (wRBP1.0). We predict that as many as 887 (4.4%) of C. elegans …


Molecular Basis Of Rna Recognition By The Embryonic Polarity Determinant Mex-5, John Pagano, Brian Farley, Lisa Mccoig, Sean Ryder May 2015

Molecular Basis Of Rna Recognition By The Embryonic Polarity Determinant Mex-5, John Pagano, Brian Farley, Lisa Mccoig, Sean Ryder

Sean P. Ryder

Embryonic development requires maternal proteins and RNA. In Caenorhabditis elegans, a gradient of CCCH tandem zinc finger (TZF) proteins coordinates axis polarization and germline differentiation. These proteins govern expression from maternal mRNAs by an unknown mechanism. Here we show that the TZF protein MEX-5, a primary anterior determinant, is an RNA-binding protein that recognizes linear RNA sequences with high affinity but low specificity. The minimal binding site is a tract of six or more uridines within a 9-13-nucleotide window. This sequence is remarkably abundant in the 3'-untranslated region of C. elegans transcripts, demonstrating that MEX-5 alone cannot specify mRNA target …


A Quantitative Rna Code For Mrna Target Selection By The Germline Fate Determinant Gld-1, Jane Wright, Dimos Gaidatzis, Mathias Senften, Brian Farley, Eric Westhof, Sean Ryder, Rafal Ciosk May 2015

A Quantitative Rna Code For Mrna Target Selection By The Germline Fate Determinant Gld-1, Jane Wright, Dimos Gaidatzis, Mathias Senften, Brian Farley, Eric Westhof, Sean Ryder, Rafal Ciosk

Sean P. Ryder

RNA-binding proteins (RBPs) are critical regulators of gene expression. To understand and predict the outcome of RBP-mediated regulation a comprehensive analysis of their interaction with RNA is necessary. The signal transduction and activation of RNA (STAR) family of RBPs includes developmental regulators and tumour suppressors such as Caenorhabditis elegans GLD-1, which is a key regulator of germ cell development. To obtain a comprehensive picture of GLD-1 interactions with the transcriptome, we identified GLD-1-associated mRNAs by RNA immunoprecipitation followed by microarray detection. Based on the computational analysis of these mRNAs we generated a predictive model, where GLD-1 association with mRNA is …


Rna Target Specificity Of The Embryonic Cell Fate Determinant Pos-1, Brian Farley, John Pagano, Sean Ryder May 2015

Rna Target Specificity Of The Embryonic Cell Fate Determinant Pos-1, Brian Farley, John Pagano, Sean Ryder

Sean P. Ryder

Specification of Caenorhabditis elegans body axes and cell fates occurs prior to the activation of zygotic transcription. Several CCCH-type tandem zinc finger (TZF) proteins coordinate local activation of quiescent maternal mRNAs after fertilization, leading to asymmetric expression of factors required for patterning. The primary determinant of posterior fate is the TZF protein POS-1. Mutants of pos-1 are maternal effect lethal with a terminal phenotype that includes excess pharyngeal tissue and no endoderm or germline. Here, we delineate the consensus POS-1 recognition element (PRE) required for specific recognition of its target mRNAs. The PRE is necessary but not sufficient to pattern …


Fbf Represses The Cip/Kip Cell-Cycle Inhibitor Cki-2 To Promote Self-Renewal Of Germline Stem Cells In C. Elegans, Irene Kalchhauser, Brian Farley, Sandra Pauli, Sean Ryder, Rafal Ciosk May 2015

Fbf Represses The Cip/Kip Cell-Cycle Inhibitor Cki-2 To Promote Self-Renewal Of Germline Stem Cells In C. Elegans, Irene Kalchhauser, Brian Farley, Sandra Pauli, Sean Ryder, Rafal Ciosk

Sean P. Ryder

Although the decision between stem cell self-renewal and differentiation has been linked to cell-cycle modifications, our understanding of cell-cycle regulation in stem cells is very limited. Here, we report that FBF/Pumilio, a conserved RNA-binding protein, promotes self-renewal of germline stem cells by repressing CKI-2(Cip/Kip), a Cyclin E/Cdk2 inhibitor. We have previously shown that repression of CYE-1 (Cyclin E) by another RNA-binding protein, GLD-1/Quaking, promotes germ cell differentiation. Together, these findings suggest that a post-transcriptional regulatory circuit involving FBF and GLD-1 controls the self-renewal versus differentiation decision in the germline by promoting high CYE-1/CDK-2 activity in stem cells, and inhibiting CYE-1/CDK-2 …


The Regulation Of Genes And Genomes By Small Rnas., Victor Ambros, Xuemei Chen Apr 2007

The Regulation Of Genes And Genomes By Small Rnas., Victor Ambros, Xuemei Chen

Victor R. Ambros

A recent Keystone Symposium on 'MicroRNAs and siRNAs: Biological Functions and Mechanisms' was organized by David Bartel and Shiv Grewal (and was held in conjunction with 'RNAi for Target Validation and as a Therapeutic', organized by Stephen Friend and John Maraganore). The 'MicroRNAs and siRNAs' meeting brought together scientists working on diverse biological aspects of small regulatory RNAs, including microRNAs, small interfering RNAs (siRNAs) and Piwi-interacting RNAs (piRNAs and rasiRNAs). Among the themes discussed were the diversity of small regulatory RNAs and their developmental functions, their biogenesis, the identification of their regulatory targets, their mechanisms of action, and their roles …


Potent Effect Of Target Structure On Microrna Function, Peter Williams, Dang Long, Rosalind Lee, Chi Chan, Victor Ambros, Ye Ding Mar 2007

Potent Effect Of Target Structure On Microrna Function, Peter Williams, Dang Long, Rosalind Lee, Chi Chan, Victor Ambros, Ye Ding

Victor R. Ambros

MicroRNAs (miRNAs) are small noncoding RNAs that repress protein synthesis by binding to target messenger RNAs. We investigated the effect of target secondary structure on the efficacy of repression by miRNAs. Using structures predicted by the Sfold program, we model the interaction between an miRNA and a target as a two-step hybridization reaction: nucleation at an accessible target site followed by hybrid elongation to disrupt local target secondary structure and form the complete miRNA-target duplex. This model accurately accounts for the sensitivity to repression by let-7 of various mutant forms of the Caenorhabditis elegans lin-41 3' untranslated region and for …


The 2007 George W. Beadle Medal. Robert K. Herman., Victor Ambros Jan 2007

The 2007 George W. Beadle Medal. Robert K. Herman., Victor Ambros

Victor R. Ambros

No abstract provided.


Developmental Biology. Encountering Micrornas In Cell Fate Signaling., Xantha Karp, Victor Ambros Nov 2005

Developmental Biology. Encountering Micrornas In Cell Fate Signaling., Xantha Karp, Victor Ambros

Victor R. Ambros

Comment on: LIN-12/Notch activation leads to microRNA-mediated down-regulation of Vav in C. elegans. [Science. 2005]


The C. Elegans Heterochronic Gene Lin-46 Affects Developmental Timing At Two Larval Stages And Encodes A Relative Of The Scaffolding Protein Gephyrin., Anita Pepper, Jill Mccane, Kevin Kemper, Denise Yeung, Rosalind Lee, Victor Ambros, Eric Moss Apr 2004

The C. Elegans Heterochronic Gene Lin-46 Affects Developmental Timing At Two Larval Stages And Encodes A Relative Of The Scaffolding Protein Gephyrin., Anita Pepper, Jill Mccane, Kevin Kemper, Denise Yeung, Rosalind Lee, Victor Ambros, Eric Moss

Victor R. Ambros

The succession of developmental events in the C. elegans larva is governed by the heterochronic genes. When mutated, these genes cause either precocious or retarded developmental phenotypes, in which stage-specific patterns of cell division and differentiation are either skipped or reiterated, respectively. We identified a new heterochronic gene, lin-46, from mutations that suppress the precocious phenotypes caused by mutations in the heterochronic genes lin-14 and lin-28. lin-46 mutants on their own display retarded phenotypes in which cell division patterns are reiterated and differentiation is prevented in certain cell lineages. Our analysis indicates that lin-46 acts at a step immediately downstream …


Microrna Pathways In Flies And Worms: Growth, Death, Fat, Stress, And Timing, Victor Ambros Jun 2003

Microrna Pathways In Flies And Worms: Growth, Death, Fat, Stress, And Timing, Victor Ambros

Victor R. Ambros

Drosophila geneticists have uncovered roles for microRNAs in the coordination of cell proliferation and cell death during development, and in stress resistance and fat metabolism. In C. elegans, a homolog of the well-known fly developmental regulator hunchback acts downstream of the microRNAs lin-4 and let-7 in a pathway controlling developmental timing.


Micrornas And Other Tiny Endogenous Rnas In C. Elegans, Victor Ambros, Rosalind Lee, Ann Lavanway, Peter Williams, David Jewell May 2003

Micrornas And Other Tiny Endogenous Rnas In C. Elegans, Victor Ambros, Rosalind Lee, Ann Lavanway, Peter Williams, David Jewell

Victor R. Ambros

BACKGROUND: MicroRNAs (miRNAs) are small noncoding RNAs that are processed from hairpin precursor transcripts by Dicer. miRNAs probably inhibit translation of mRNAs via imprecise antisense base-pairing. Small interfering RNAs (siRNAs) are similar in size to miRNAs, but they recognize targets by precise complementarity and elicit RNA-mediated interference (RNAi). We employed cDNA sequencing and comparative genomics to identify additional C. elegans small RNAs with properties similar to miRNAs and siRNAs. RESULTS: We found three broad classes of small RNAs in C. elegans: (1) 21 new miRNA genes (we estimate that C. elegans contains approximately 100 distinct miRNA genes, about 30% of …


An Extensive Class Of Small Rnas In Caenorhabditis Elegans, Rosalind Lee, Victor Ambros Oct 2001

An Extensive Class Of Small Rnas In Caenorhabditis Elegans, Rosalind Lee, Victor Ambros

Victor R. Ambros

The lin-4 and let-7 antisense RNAs are temporal regulators that control the timing of developmental events in Caenorhabditis elegans by inhibiting translation of target mRNAs. let-7 RNA is conserved among bilaterian animals, suggesting that this class of small RNAs [microRNAs (miRNAs)] is evolutionarily ancient. Using bioinformatics and cDNA cloning, we found 15 new miRNA genes in C. elegans. Several of these genes express small transcripts that vary in abundance during C. elegans larval development, and three of them have apparent homologs in mammals and/or insects. Small noncoding RNAs of the miRNA class appear to be numerous and diverse.


The Temporal Control Of Cell Cycle And Cell Fate In Caenorhabditis Elegans, Victor Ambros Dec 2000

The Temporal Control Of Cell Cycle And Cell Fate In Caenorhabditis Elegans, Victor Ambros

Victor R. Ambros

The nematode Caenorhabditis elegans develops through two major phases: the first phase, embryogenesis, consists of a rapid series of cleavage cell divisions leading to morphogenesis of a first stage larva. The second phase is postembryonic development, which consists of developmentally regulated cell cycles that occur during the four larval stages leading to the adult. Precursor cells set aside during embryogenesis divide through stereotypical cell lineage patterns during the four larval stages to generate larval and adult structures. The precise timing of the postembryonic cell divisions is under strict control, in most cases with a developmentally regulated G1. In certain postembryonic …


Control Of Developmental Timing In Caenorhabditis Elegans, Victor Ambros Jul 2000

Control Of Developmental Timing In Caenorhabditis Elegans, Victor Ambros

Victor R. Ambros

Studies of the nematode Caenorhabditis elegans have identified genetic and molecular mechanisms controlling temporal patterns of developmental events. Mutations in genes of the C. elegans heterochronic pathway cause altered temporal patterns of larval development, in which cells at certain larval stages execute cell division patterns or differentiation programs normally specific for other stages. The products of the heterochronic genes include transcriptional and translational regulators and two different cases of novel small translational regulatory RNAs. Other genes of the pathway encode evolutionarily conserved proteins, including a homolog of the Drosophila Period circadian timing regulator, and a member of the nuclear receptor …


The Lin-41 Rbcc Gene Acts In The C. Elegans Heterochronic Pathway Between The Let-7 Regulatory Rna And The Lin-29 Transcription Factor, Frank Slack, Michael Basson, Zhongchi Liu, Victor Ambros, H. Horvitz, Gary Ruvkun Mar 2000

The Lin-41 Rbcc Gene Acts In The C. Elegans Heterochronic Pathway Between The Let-7 Regulatory Rna And The Lin-29 Transcription Factor, Frank Slack, Michael Basson, Zhongchi Liu, Victor Ambros, H. Horvitz, Gary Ruvkun

Victor R. Ambros

Null mutations in the C. elegans heterochronic gene lin-41 cause precocious expression of adult fates at larval stages. Increased lin-41 activity causes the opposite phenotype, reiteration of larval fates. let-7 mutations cause similar reiterated heterochronic phenotypes that are suppressed by lin-41 mutations, showing that lin-41 is negatively regulated by let-7. lin-41 negatively regulates the timing of LIN-29 adult specification transcription factor expression. lin-41 encodes an RBCC protein, and two elements in the lin-413'UTR are complementary to the 21 nucleotide let-7 regulatory RNA. A lin-41::GFP fusion gene is downregulated in the tissues affected by lin-41 at the time that the let-7 …


The Lin-4 Regulatory Rna Controls Developmental Timing In Caenorhabditis Elegans By Blocking Lin-14 Protein Synthesis After The Initiation Of Translation, Philip Olsen, Victor Ambros Dec 1999

The Lin-4 Regulatory Rna Controls Developmental Timing In Caenorhabditis Elegans By Blocking Lin-14 Protein Synthesis After The Initiation Of Translation, Philip Olsen, Victor Ambros

Victor R. Ambros

lin-4 encodes a small RNA that is complementary to sequences in the 3' untranslated region (UTR) of lin-14 mRNA and that acts to developmentally repress the accumulation of LIN-14 protein. This repression is essential for the proper timing of numerous events of Caenorhabditis elegans larval development. We have investigated the mechanism of lin-4 RNA action by examining the fate of lin-14 mRNA in vivo during the time that lin-4 RNA is expressed. Our results indicate that the rate of synthesis of lin-14 mRNA, its state of polyadenylation, its abundance in the cytoplasmic fraction, and its polysomal sedimentation profile do not …


The Timing Oflin-4rna Accumulation Controls The Timing Of Postembryonic Developmental Events Incaenorhabditis Elegans, Rhonda Feinbaum, Victor Ambros May 1999

The Timing Oflin-4rna Accumulation Controls The Timing Of Postembryonic Developmental Events Incaenorhabditis Elegans, Rhonda Feinbaum, Victor Ambros

Victor R. Ambros

The lin-4 gene encodes a small RNA that is required to translationally repress lin-14 toward the end of the first larval stage of Caenorhabditis elegans development. To determine if the timing of LIN-14 protein down-regulation depends on the temporal profile of lin-4 RNA level, we analyzed the stage-specificity of lin-4 RNA expression during wild-type development and examined the phenotypes of transgenic worms that overexpress lin-4 RNA during the first larval stage. We found that lin-4 RNA first becomes detectable at approximately 12 h of wild-type larval development and rapidly accumulates to nearly maximum levels by 16 h. This profile of …


Cell Cycle-Dependent Sequencing Of Cell Fate Decisions In Caenorhabditis Elegans Vulva Precursor Cells, Victor Ambros Apr 1999

Cell Cycle-Dependent Sequencing Of Cell Fate Decisions In Caenorhabditis Elegans Vulva Precursor Cells, Victor Ambros

Victor R. Ambros

In Caenorhabditis elegans, the fates of the six multipotent vulva precursor cells (VPCs) are specified by extracellular signals. One VPC expresses the primary (1 degrees ) fate in response to a Ras-mediated inductive signal from the gonad. The two VPCs flanking the 1 degrees cell each express secondary (2 degrees ) fates in response to lin-12-mediated lateral signaling. The remaining three VPCs each adopt the non-vulval tertiary (3 degrees ) fate. Here I describe experiments examining how the selection of these vulval fates is affected by cell cycle arrest and cell cycle-restricted lin-12 activity. The results suggest that lin-12 participates …


Developmental Regulation Of A Cyclin-Dependent Kinase Inhibitor Controls Postembryonic Cell Cycle Progression In Caenorhabditis Elegans, Yang Hong, Richard Roy, Victor Ambros Aug 1998

Developmental Regulation Of A Cyclin-Dependent Kinase Inhibitor Controls Postembryonic Cell Cycle Progression In Caenorhabditis Elegans, Yang Hong, Richard Roy, Victor Ambros

Victor R. Ambros

C. elegans cki-1 encodes a member of the CIP/KIP family of cyclin-dependent kinase inhibitors, and functions to link postembryonic developmental programs to cell cycle progression. The expression pattern of cki-1::GFP suggests that cki-1 is developmentally regulated in blast cells coincident with G1, and in differentiating cells. Ectopic expression of CKI-1 can prematurely arrest cells in G1, while reducing cki-1 activity by RNA-mediated interference (RNAi) causes extra larval cell divisions, suggesting a role for cki-1 in the developmental control of G1/S. cki-1 activity is required for the suspension of cell cycling that occurs in dauer larvae and starved L1 larvae in …