To maintain tissue homeostasis, some organs are able to replace dying cells with additional proliferation of surviving cells. Such proliferation can be localized ( e.g. , a regeneration blastema) or diffuse (compensatory growth). The relationship between such growth and the growth that occurs during development has not been characterized in detail. Drosophila melanogaster larval imaginal discs can recover from extensive damage, producing normally sized adult organs. Here we describe a system using genetic mosaics to screen for recessive mutations that impair compensatory growth. By generating clones of cells that carry a temperature-sensitive cell-lethal mutation, we conditionally ablate patches of tissue in the imaginal disc and assess the ability of the surviving sister clones to replace the lost tissue. We have used this system together with a modified whole-genome resequencing (WGS) strategy to identify several mutations that selectively compromise compensatory growth. We find specific alleles of bunched ( bun ) and Ribonucleoside diphosphate reductase large subunit ( RnrL ) reduce compensatory growth in the imaginal disc. Other genes identified in the screen, including two alleles of Topoisomerase 3-alpha ( Top3α ), while also required for developmental growth, appear to have an enhanced requirement during compensatory growth. Compensatory growth occurs at a higher rate than normal growth and may therefore have features in common with some types of overgrowth. Indeed, the RnrL allele identified compromises both these types of altered growth and mammalian ribonucleotide reductase and topoisomerases are targets of anticancer drugs. Finally, the approach we describe is applicable to the study of compensatory growth in diverse tissues in Drosophila . Received July 21, 2011. Accepted September 12, 2011. Copyright © 2011 by the Genetics Society of America Available freely online through the author-supported open access option. « Previous | Next Article » Table of Contents OPEN ACCESS ARTICLE This Article Published online before print September 16, 2011 , doi: 10.1534/genetics.111.132993 Genetics December 1, 2011 vol. 189 no. 4 1309-1326 Free via Open Access: OA » Abstract OA Full Text Full Text (PDF) Supporting Information Classifications Investigations Developmental and Behavioral Genetics Services Email this article to a friend Alert me when this article is cited Alert me if a correction is posted Similar articles in this journal Similar articles in Web of Science Similar articles in PubMed Download to citation manager Citing Articles Load citing article information Google Scholar Articles by Gerhold, A. R. PubMed PubMed citation Articles by Gerhold, A. R. Related Content Load related web page information This Months's Issue December 2011, 189 (4) Alert me to new issues of Genetics ABOUT SUBSCRIBE INFO FOR AUTHORS ONLINE SUBMISSION EDITORIAL BOARD CONTACT ALERTS HELP ADVERTISING RSS Help Contact Us International Access Link Print ISSN: 0016-6731 Online ISSN: 1943-2631 Copyright © 2011 by the Genetics Society of America phone: 412-268-1812 fax: 412-268-1813 email: genetics-gsa@andrew.cmu.edu

/lp/genetics-society-of-america/identification-and-characterization-of-genes-required-for-compensatory-QjZhlXRNW4