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      The great small organisms of developmental genetics: Caenorhabditis elegans and Drosophila melanogaster

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          Abstract

          Experimental embryologists working at the turn of the 19th century suggested fundamental mechanisms of development, such as localized cytoplasmic determinants and tissue induction. However, the molecular basis underlying these processes proved intractable for a long time, despite concerted efforts in many developmental systems to isolate factors with a biological role. That road block was overcome by combining developmental biology with genetics. This powerful approach used unbiased genome-wide screens to isolate mutants with developmental defects and to thereby identify genes encoding key determinants and regulatory pathways that govern development. Two small invertebrates were the pioneers: the fruit fly Drosophila melanogaster and the nematode Caenorhabditis elegans. Their modes of development differ in many ways, but the two together led the way to unraveling the molecular mechanisms of many fundamental developmental processes. The discovery of the grand homologies between key players in development throughout the animal kingdom underscored the usefulness of studying these small invertebrate models for animal development and even human disease. We describe developmental genetics in Drosophila and C. elegans up to the rise of genomics at the beginning of the 21st Century. Finally, we discuss themes that emerge from the histories of such distinct organisms and prospects of this approach for the future.

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          THE GENETICS OF CAENORHABDITIS ELEGANS

          Methods are described for the isolation, complementation and mapping of mutants of Caenorhabditis elegans, a small free-living nematode worm. About 300 EMS-induced mutants affecting behavior and morphology have been characterized and about one hundred genes have been defined. Mutations in 77 of these alter the movement of the animal. Estimates of the induced mutation frequency of both the visible mutants and X chromosome lethals suggests that, just as in Drosophila, the genetic units in C.elegans are large.
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            The C. elegans heterochronic gene lin-4 encodes small RNAs with antisense complementarity to lin-14

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              Potent and specific genetic interference by double-stranded RNA in Caenorhabditis elegans.

              Experimental introduction of RNA into cells can be used in certain biological systems to interfere with the function of an endogenous gene. Such effects have been proposed to result from a simple antisense mechanism that depends on hybridization between the injected RNA and endogenous messenger RNA transcripts. RNA interference has been used in the nematode Caenorhabditis elegans to manipulate gene expression. Here we investigate the requirements for structure and delivery of the interfering RNA. To our surprise, we found that double-stranded RNA was substantially more effective at producing interference than was either strand individually. After injection into adult animals, purified single strands had at most a modest effect, whereas double-stranded mixtures caused potent and specific interference. The effects of this interference were evident in both the injected animals and their progeny. Only a few molecules of injected double-stranded RNA were required per affected cell, arguing against stochiometric interference with endogenous mRNA and suggesting that there could be a catalytic or amplification component in the interference process.
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                Author and article information

                Journal
                0372762
                3389
                Dev Biol
                Dev Biol
                Developmental biology
                0012-1606
                1095-564X
                4 May 2022
                May 2022
                02 March 2022
                11 May 2022
                : 485
                : 93-122
                Affiliations
                [a ]University of Wisconsin-Madison, Department of Biochemistry, USA
                [b ]Max-Planck-Institute for Biology Tübingen, Germany
                Author notes
                [* ]Corresponding author. cnv@ 123456tuebingen.mpg.de (C. Nüsslein-Volhard)
                [** ]Corresponding author. jekimble@ 123456wisc.edu (J. Kimble)
                Article
                NIHMS1801351
                10.1016/j.ydbio.2022.02.013
                9092520
                35247454
                709c31df-4a53-4c37-9b47-2089996c3f2e

                This is an open access article under the CC BY-NC-ND license ( http://creativecommons.org/licenses/by-nc-nd/4.0/).

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                Categories
                Article

                Developmental biology
                genetic screens,mutagenesis,embryogenesis,morphogen,pattern formation
                Developmental biology
                genetic screens, mutagenesis, embryogenesis, morphogen, pattern formation

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