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Costa M, Hunter CP, Harris JM, Maloof JN, Mueller-Immergluck MM, Salser SJ, Cowing DW, Wang BB, Austin JA, Honigberg LA, Kenyon CJ, Waring DA, Wrischnik LA
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Cold Spring Harb Symp Quant Biol,
1997]
Hox mutations are fascinating. Like magic, they can turn antennae into legs or create extra wings. What makes these genes so talented? How can they make such high-level decisions? Are there simple rules that can explain the effects they have on the development of individual cells? Do the genes act multiple times during the development of a tissue to micromanage individual cell fate decisions, or can they act relatively early to initiate developmental programs that run independently of their further input?
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[
Nature,
2003]
Studies of worms have revealed hundreds of proteins that, when mutated, extend lifespan. Can this work tell us anything about mammalian ageing? A look at the effects of one such protein on lab mice suggests that it can.
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[
Epigenomes,
2022]
Transgenerational inheritance can occur at telomeres in distinct contexts. Deficiency for telomerase or telomere-binding proteins in germ cells can result in shortened or lengthened chromosome termini that are transmitted to progeny. In human families, altered telomere lengths can result in stem cell dysfunction or tumor development. Genetic inheritance of altered telomeres as well as mutations that alter telomeres can result in progressive telomere length changes over multiple generations. Telomeres of yeast can modulate the epigenetic state of subtelomeric genes in a manner that is mitotically heritable, and the effects of telomeres on subtelomeric gene expression may be relevant to senescence or other human adult-onset disorders. Recently, two novel epigenetic states were shown to occur at <i>C. elegans</i> telomeres, where very low or high levels of telomeric protein foci can be inherited for multiple generations through a process that is regulated by histone methylation.Together, these observations illustrate that information relevant to telomere biology can be inherited via genetic and epigenetic mechanisms, although the broad impact of epigenetic inheritance to human biology remains unclear.
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[
Curr Biol,
1999]
Wnt signalling controls many different cell fate choices in a wide variety of animal species. Recent studies have revealed that regulatory interactions at several steps in the pathway can modify its outcome, helping to explain how the same pathway can, in different contexts, have very different characteristics and consequences.
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[
Nature,
2010]
The nematode Caenorhabditis elegans ages and dies in a few weeks, but humans can live for 100 years or more. Assuming that the ancestor we share with nematodes aged rapidly, this means that over evolutionary time mutations have increased lifespan more than 2,000-fold. Which genes can extend lifespan? Can we augment their activities and live even longer? After centuries of wistful poetry and wild imagination, we are now getting answers, often unexpected ones, to these fundamental questions.
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[
WormBook,
2005]
Genetic suppression has provided a very powerful tool for analyzing C. elegans. Suppression experiments are facilitated by the ability to handle very large numbers of individuals and to apply powerful selections. Because the animal grows as a self-fertilizing diploid, both dominant and recessive suppressors can be recovered. Many different kinds of suppression have been reported. These are discussed by category, with examples, together with discussion of how suppressors can be used to interpret the underlying biology, and to enable further experimentation. Suppression phenomena can be divided into intragenic and extragenic classes, depending on whether the suppressor lies in the same gene as the starting mutation, or in a different gene. Intragenic types include same-site replacement, compensatory mutation, alteration in splicing, and reversion of dominant mutations by cis- knockout. Extragenic suppression can occur by a variety of informational mechanisms, such as alterations in splicing, translation or nonsense-mediated decay. In addition, extragenic suppression can occur by bypass, dosage effects, product interaction, or removal of toxic products. Within signaling pathways, suppression can occur by modulating the strength of signal transmission, or by epistatic interactions that can reveal the underlying regulatory hierarchies. In C. elegans biology, the processes of muscle development, vulva formation and sex determination have provided remarkably rich arenas for the investigation and exploitation of suppression.
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[
Trends Genet,
1999]
Species throughout the animal kingdom share not only housekeeping but also many key regulatory genes. Nonetheless, species differ from one another developmentally and thus, also morphologically. One of the general aims of comparative developmental genetics is to understand how similar molecules can generate the known diversity of biological form. Here, we argue that gene function can change in different ways during the evolution of developmental processes. Genes can be recruited to serve completely new functions in a new regulatory linkage (co-option), they can change their molecular specificity while remaining in the original (homologous) developmental program and can, at the same time, retain other functions. We describe evidence for such evolutionary patterns based on the comparison of loss-of-function mutations of homologous genes of the two free-living nematodes Caenorhabditis elegans and Pristionchus pacificus. Ultimately, it is the interplay of conservation and change of the specificity of genes and genetic networks that generates developmental novelty over evolutionary time.
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[
Genome Biol,
2008]
ABSTRACT: 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.
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[
Epigenetics,
2014]
While most eukaryotic genomes contain transposable elements that can provide select evolutionary advantages to a given organism, failure to tightly control the mobility of such transposable elements can result in compromised genomic integrity of both parental and subsequent generations. Together with the Piwi subfamily of Argonaute proteins, small, non-coding Piwi-interacting RNAs (piRNAs) primarily function in the germ line to defend the genome against the potentially deleterious effects that can be caused by transposition. Here, we describe recent discoveries concerning the biogenesis and function of piRNAs in the nematode Caenorhabditis elegans, illuminating how the faithful production of these mature species can impart a robust defense mechanism for the germ line to counteract problems caused by foreign genetic elements across successive generations by contributing to the epigenetic memory of non-self vs. self.
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[
Front Physiol,
2014]
We describe a strategy for exploring the function of protein-protein interactions in striated muscle in vivo. We describe our experience using this strategy to study the interaction of UNC-112 (kindlin) with PAT-4 (integrin linked kinase). Random mutagenesis is used to generate a collection of mutants that are screened for lack of binding or gain of binding using a yeast 2-hybrid assay. The mutant proteins are then expressed in transgenic C. elegans to determine their ability to localize in the sarcomere. We emphasize two advantages of this strategy: (1) for studying the interaction of protein A with protein B, when protein A can interact with multiple proteins, and (2) it explores the function of an interaction rather than the absence of, or reduced level of, a protein as can be obtained with null mutants or knockdown by RNAi. We propose that this method can be generalized for studying the meaning of a protein-protein interaction in muscle for any system in which transgenic animals can be generated and their muscles can be imaged.