Genetic Screen in Drosophila Melanogaster Uncovers a Novel Set of Genes Required for Embryonic Epithelial Repair

Overview

Journal Genetics

Publisher Oxford University Press

Specialty Genetics

Date 2009 Nov 4

PMID 19884309

Citations 45

Authors

Isabel Campos

Jennifer A Geiger

Ana Catarina Santos

Vanessa Carlos

Antonio Jacinto

Affiliations

Soon will be listed here.

Abstract

The wound healing response is an essential mechanism to maintain the integrity of epithelia and protect all organisms from the surrounding milieu. In the "purse-string" mechanism of wound closure, an injured epithelial sheet cinches its hole closed via an intercellular contractile actomyosin cable. This process is conserved across species and utilized by both embryonic as well as adult tissues, but remains poorly understood at the cellular level. In an effort to identify new players involved in purse-string wound closure we developed a wounding strategy suitable for screening large numbers of Drosophila embryos. Using this methodology, we observe wound healing defects in Jun-related antigen (encoding DJUN) and scab (encoding Drosophila alphaPS3 integrin) mutants and performed a forward genetics screen on the basis of insertional mutagenesis by transposons that led to the identification of 30 lethal insertional mutants with defects in embryonic epithelia repair. One of the mutants identified is an insertion in the karst locus, which encodes Drosophila beta(Heavy)-spectrin. We show beta(Heavy)-spectrin (beta(H)) localization to the wound edges where it presumably exerts an essential function to bring the wound to normal closure.

Citing Articles

Viruses in Laboratory and Their Impact on Host Gene Expression.

Kuyateh O, Obbard D Viruses. 2023; 15(9).

PMID: 37766256 PMC: 10537266. DOI: 10.3390/v15091849.

CAF-1 and Rtt101p function within the replication-coupled chromatin assembly network to promote H4 K16ac, preventing ectopic silencing.

Young T, Cui Y, Pfeffer C, Hobbs E, Liu W, Irudayaraj J PLoS Genet. 2020; 16(12):e1009226.

PMID: 33284793 PMC: 7746308. DOI: 10.1371/journal.pgen.1009226.

Drp1-mediated mitochondrial fission regulates calcium and F-actin dynamics during wound healing.

Ponte S, Carvalho L, Gagliardi M, Campos I, Oliveira P, Jacinto A Biol Open. 2020; 9(5).

PMID: 32184231 PMC: 7225088. DOI: 10.1242/bio.048629.

is essential for JNK pathway activation and wound closure in .

Lee C, Kwon Y, Lee Y, Park M, Choe K Mol Biol Cell. 2019; 30(21):2651-2658.

PMID: 31483695 PMC: 6761768. DOI: 10.1091/mbc.E18-12-0822.

Simu-dependent clearance of dying cells regulates macrophage function and inflammation resolution.

Roddie H, Armitage E, Coates J, Johnston S, Evans I PLoS Biol. 2019; 17(5):e2006741.

PMID: 31086359 PMC: 6516643. DOI: 10.1371/journal.pbio.2006741.

References

Zink B, Paro R . In vivo binding pattern of a trans-regulator of homoeotic genes in Drosophila melanogaster. Nature. 1989; 337(6206):468-71. DOI: 10.1038/337468a0. View

Spradling A, Stern D, Beaton A, Rhem E, Laverty T, Mozden N . The Berkeley Drosophila Genome Project gene disruption project: Single P-element insertions mutating 25% of vital Drosophila genes. Genetics. 1999; 153(1):135-77. PMC: 1460730. DOI: 10.1093/genetics/153.1.135. View

Smith E, Winter B, Eissenberg J, Shilatifard A . Regulation of the transcriptional activity of poised RNA polymerase II by the elongation factor ELL. Proc Natl Acad Sci U S A. 2008; 105(25):8575-9. PMC: 2438402. DOI: 10.1073/pnas.0804379105. View

FRANK L, Rushlow C . A group of genes required for maintenance of the amnioserosa tissue in Drosophila. Development. 1996; 122(5):1343-52. DOI: 10.1242/dev.122.5.1343. View

Stark K, Yee G, Roote C, Williams E, ZUSMAN S, Hynes R . A novel alpha integrin subunit associates with betaPS and functions in tissue morphogenesis and movement during Drosophila development. Development. 1997; 124(22):4583-94. DOI: 10.1242/dev.124.22.4583. View

Heinze M, Kofler M, Freund C . Investigating the functional role of CD2BP2 in T cells. Int Immunol. 2007; 19(11):1313-8. DOI: 10.1093/intimm/dxm100. View

Scott R, Schuldiner O, Neufeld T . Role and regulation of starvation-induced autophagy in the Drosophila fat body. Dev Cell. 2004; 7(2):167-78. DOI: 10.1016/j.devcel.2004.07.009. View

Li G, Gustafson-Brown C, Hanks S, Nason K, Arbeit J, Pogliano K . c-Jun is essential for organization of the epidermal leading edge. Dev Cell. 2003; 4(6):865-77. DOI: 10.1016/s1534-5807(03)00159-x. View

Galko M, Krasnow M . Cellular and genetic analysis of wound healing in Drosophila larvae. PLoS Biol. 2004; 2(8):E239. PMC: 479041. DOI: 10.1371/journal.pbio.0020239. View

10.

Pearson J, Juarez M, Kim M, Drivenes O, McGinnis W . Multiple transcription factor codes activate epidermal wound-response genes in Drosophila. Proc Natl Acad Sci U S A. 2009; 106(7):2224-9. PMC: 2630199. DOI: 10.1073/pnas.0810219106. View

11.

Mace K, Pearson J, McGinnis W . An epidermal barrier wound repair pathway in Drosophila is mediated by grainy head. Science. 2005; 308(5720):381-5. DOI: 10.1126/science.1107573. View

12.

Tarnay J, Szeri F, Ilias A, Annilo T, Sung C, Le Saux O . The dMRP/CG6214 gene of Drosophila is evolutionarily and functionally related to the human multidrug resistance-associated protein family. Insect Mol Biol. 2004; 13(5):539-48. DOI: 10.1111/j.0962-1075.2004.00512.x. View

13.

Young P, Richman A, KETCHUM A, Kiehart D . Morphogenesis in Drosophila requires nonmuscle myosin heavy chain function. Genes Dev. 1993; 7(1):29-41. DOI: 10.1101/gad.7.1.29. View

14.

Schock F, Perrimon N . Retraction of the Drosophila germ band requires cell-matrix interaction. Genes Dev. 2003; 17(5):597-602. PMC: 196012. DOI: 10.1101/gad.1068403. View

15.

Nusslein-Volhard C, Wieschaus E, Kluding H . Mutations affecting the pattern of the larval cuticle inDrosophila melanogaster : I. Zygotic loci on the second chromosome. Wilehm Roux Arch Dev Biol. 2017; 193(5):267-282. DOI: 10.1007/BF00848156. View

16.

Wilson R, Goodman J, Strelets V . FlyBase: integration and improvements to query tools. Nucleic Acids Res. 2007; 36(Database issue):D588-93. PMC: 2238994. DOI: 10.1093/nar/gkm930. View

17.

Uv A, Harrison E, Bray S . Tissue-specific splicing and functions of the Drosophila transcription factor Grainyhead. Mol Cell Biol. 1997; 17(11):6727-35. PMC: 232527. DOI: 10.1128/MCB.17.11.6727. View

18.

Ting S, Caddy J, Wilanowski T, Auden A, Cunningham J, Elias P . The epidermis of grhl3-null mice displays altered lipid processing and cellular hyperproliferation. Organogenesis. 2009; 2(2):33-5. PMC: 2634083. DOI: 10.4161/org.2.2.2167. View

19.

McKeown C, Praitis V, Austin J . sma-1 encodes a betaH-spectrin homolog required for Caenorhabditis elegans morphogenesis. Development. 1998; 125(11):2087-98. DOI: 10.1242/dev.125.11.2087. View

20.

De Gregorio E, Spellman P, Rubin G, Lemaitre B . Genome-wide analysis of the Drosophila immune response by using oligonucleotide microarrays. Proc Natl Acad Sci U S A. 2001; 98(22):12590-5. PMC: 60098. DOI: 10.1073/pnas.221458698. View