Digital Commons Network^™

The Functions Of Animal Micrornas., Victor Ambros

Victor R. Ambros

MicroRNAs (miRNAs) are small RNAs that regulate the expression of complementary messenger RNAs. Hundreds of miRNA genes have been found in diverse animals, and many of these are phylogenetically conserved. With miRNA roles identified in developmental timing, cell death, cell proliferation, haematopoiesis and patterning of the nervous system, evidence is mounting that animal miRNAs are more numerous, and their regulatory impact more pervasive, than was previously suspected.

The Caenorhabditis Elegans F-Box Protein Sel-10 Promotes Female Development And May Target Fem-1 And Fem-3 For Degradation By The Proteasome, Sibylle Jager, Hillel T. Schwartz, H. Robert Horvitz, Barbara Conradt

Dartmouth Scholarship

The Caenorhabditis elegans F-box protein SEL-10 and its human homolog have been proposed to regulate LIN-12 Notch signaling by targeting for ubiquitin-mediated proteasomal degradation LIN-12 Notch proteins and SEL-12 PS1 presenilins, the latter of which have been implicated in Alzheimer's disease. We found that sel-10 is the same gene as egl-41, which previously had been defined by gain-of-function mutations that semidominantly cause masculinization of the hermaphrodite soma. Our results demonstrate that mutations causing loss-of-function of sel-10 also have masculinizing activity, indicating that sel-10 functions to promote female development. Genetically, sel-10 acts upstream of the genes fem-1, fem-2, and fem-3 and …

Sexually Dimorphic Effects Of Prenatal Stress On Cognition, Hormonal Responses, And Central Neurotransmitters, Rachel E. Bowman, Neil J. Maclusky, Yessenia Sarmiento, Maya Frankfurt, Marisa Gordon, Victoria N. Luine

Psychology Faculty Publications

Exposure to stress during gestation results in physiological and behavioral alterations that persist into adulthood. This study examined the effects of prenatal stress on the postnatal expression of sexually differentiated cognitive, hormonal, and neurochemical profiles in male and female rats. Pregnant dams were subjected to restraint stress three times daily for 45 min during d 14-21 of pregnancy. The offspring of control and prenatally stressed dams were tested for anxiety-related and cognitive behaviors, stress and gonadal steroid hormone levels, as well as monoamines and metabolite levels in selected brain regions. Postnatal testosterone levels (measured at 1 and 5 d) did …

Growth Rate Gradients And Extracellular Ph In Roots: How To Control An Explosion, Winfried S. Peters

Winfried S. Peters

Drawing Lines In The Sand: Even Skipped Et Al. And Parasegment Boundaries., James B. Jaynes, Miki Fujioka

Department of Biochemistry and Molecular Biology Faculty Papers

The pair-rule segmentation gene even skipped (eve) is required to activate engrailed stripes and to organize odd-numbered parasegments (PSs). The protein product Eve has been shown to be an active repressor of transcription, and recent models for Eve function suggest that activation of engrailed is indirect, but these models have not been fully tested. Here we identify the forkhead domain transcription factor Sloppy-paired as the key intermediate in the initial activation of engrailed by Eve in odd-numbered parasegments. We also analyze the roles of the transcription factors Runt and Odd-skipped in this process. Detailed analysis of engrailed and pair-rule gene …

Expression Profiling Of Mammalian Micrornas Uncovers A Subset Of Brain-Expressed Micrornas With Possible Roles In Murine And Human Neuronal Differentiation., Lorenzo F. Sempere, Sarah Freemantle, Ian Pitha-Rowe, Eric Moss, Ethan Dmitrovsky, Victor R. Ambros

Victor R. Ambros

Background The microRNAs (miRNAs) are an extensive class of small noncoding RNAs (18 to 25 nucleotides) with probable roles in the regulation of gene expression. In Caenorhabditis elegans, lin-4 and let-7 miRNAs control the timing of fate specification of neuronal and hypodermal cells during larval development. lin-4, let-7 and other miRNA genes are conserved in mammals, and their potential functions in mammalian development are under active study. Results In order to identify mammalian miRNAs that might function in development, we characterized the expression of 119 previously reported miRNAs in adult organs from mouse and human using northern blot analysis. Of …

A Short History Of A Short Rna, Victor Ambros, Rosalind Lee, Rhonda Feinbaum

Victor R. Ambros

Comment on: The C. elegans heterochronic gene lin-4 encodes small RNAs with antisense complementarity to lin-14. [Cell. 1993]

Immunity Regulatory Dnas Share Common Organizational Features In Drosophila, Kate Senger, Grant W. Armstrong, William J. Rowell, Jennifer M. Kwan, Michele Markstein, Michael Levine

Michele Markstein

Infection results in the rapid activation of immunity genes in the Drosophila fat body. Two classes of transcription factors have been implicated in this process: the REL-containing proteins, Dorsal, Dif, and Relish, and the GATA factor Serpent. Here we present evidence that REL-GATA synergy plays a pervasive role in the immune response. SELEX assays identified consensus binding sites that permitted the characterization of several immunity regulatory DNAs. The distribution of REL and GATA sites within these DNAs suggests that most or all fat-specific immunity genes contain a common organization of regulatory elements: closely linked REL and GATA binding sites positioned …

Loss-Of-Function Analysis Of Epha Receptors In Retinotectal Mapping, David Feldheim, Masaru Nakamoto, Miriam Osterfield, Nicholas Gale, Thomas Dechiara, Rajat Rohatgi, George Yancopoulos, John Flanagan

Biology Faculty Publications

EphA tyrosine kinases are thought to act as topographically specific receptors in the well-characterized projection map from the retina to the tectum. Here, we describe a loss-of-function analysis of EphA receptors in retinotectal mapping. Expressing patches of a cytoplasmically truncated EphA3 receptor in chick retina caused temporal axons to have reduced responsiveness to posterior tectal repellent activity in vitro and to shift more posteriorly within the map in vivo . A gene disruption of mouse EphA5, replacing the intracellular domain with beta-galactosidase, reduced in vitro responsiveness of temporal axons to posterior target membranes. It also caused map abnormalities in vivo …

Does Antarctic Krill Employ Body Shrinkage As An Overwintering Strategy?, Se-Jong Ju, H. Rodger Harvey, H. C. Shinn, Y. Kim, S. H. Kang

OES Faculty Publications

To determine if Antarctic krill employ body shrinkage as one of its overwintering mechanisms in the field, Euphausia superba and Euphausia crystallorophias were collected during fall and winter in and around Marguerite Bay through US Southern Ocean GLOBEC field programs during fall and winter 2001 and 2002. The relationships between the body length and weight of both krill species were exponentially correlated with no significant differences between the two species (p>0.05). The ratio between eye diameter and body length of individual krill was examined in an expectation that it could be used as an indicator of the body shrinkage …

Visualizing The Needle In The Haystack: In Situ Hybridization With Fluorescent Dendrimers, Jacquelyn Gerhart, M. Baytion, J. Perlman, C. Neely, B. Hearon, T. Nilsen, R. Getts, J. Kadushin, Mindy George-Weinstein

PCOM Scholarly Papers

In situ hybridization with 3DNA dendrimers is a novel tool for detecting low levels of mRNA in tissue sections and whole embryos. Fluorescently labeled dendrimers were used to identify cells that express mRNA for the skeletal muscle transcription factor MyoD in the early chick embryo. A small population of MyoD mRNA positive cells was found in the epiblast prior to the initiation of gastrulation, two days earlier than previously detected using enzymatic or radiolabeled probes for mRNA. When isolated from the epiblast and placed in culture, the MyoD mRNA positive cells were able to differentiate into skeletal muscle cells. These …

Identification Of Micrornas And Other Tiny Noncoding Rnas By Cdna Cloning, Victor Ambros, Rosalind Lee

Victor R. Ambros

MicroRNAs (miRNAs) and other small RNAs can be identified by cloning and sequencing cDNAs prepared from the ∼22-nt fraction of total RNA. Methods are described for the construction of cDNA libraries from small noncoding RNAs through the use of T4 RNA ligase, reverse transcriptase, and polymerase chain reaction. cDNAs are cloned in λ or plasmid vectors, and the sequences are compared to annotated genomic sequence databases, and analyzed by RNA folding programs to distinguish miRNA sequences from other small RNAs of similar size. Northern blot hybridization is used to confirm the expression of small RNAs in vivo.