A directed screen for genes involved in Drosophila blood cell activation

Carl Johan Zettervall, Ines Anderl, Michael J. Williams, Ruth Palmer, E. Kurucz, I. Andó, Dan Hultmark

Research output: Contribution to journalArticle

223 Citations (Scopus)

Abstract

An attack by a parasitic wasp activates a vigorous cellular immune response in Drosophila larvae. This response is manifested by an increased number of circulating cells, the hemocytes, and by the appearance of a specialized class of hemocyte, the lamellocytes, which participate in the encapsulation and killing of the parasite. To study the molecular mechanisms of this response, we have overexpressed different genes in the hemocytes, by using the GAL4-upstream activating sequence system and a hemocyte-specific Hemese-GAL4 driver. Multiple transgenes were tested, representing several important signaling pathways. We found that the proliferation response and the activation of lamellocyte formation are independent phenomena. A drastic increase in the number of circulating hemocytes is caused by receptor tyrosine kinases, such as Egfr, Pvr, and Alk, as well as by the downstream signaling components Ras85D and pointed, supporting the notion that the Ras-mitogen-activated protein kinase pathway regulates hemocyte numbers. In the case of Pvr and Alk, this phenotype also is accompanied by lamellocyte formation. By contrast, constitutively active hopscotch and hemipterous give massive activation of lamellocyte formation with little or no increase in total hemocyte numbers. This finding indicates that both the Jak/Stat and the Jun kinase pathways affect lamellocyte formation. Still other signals, mediated by aopACT, Toll10b, and Rac1 expression, cause a simultaneous increase in lamellocyte and total cell numbers, and the same effect is seen when WNT signaling is suppressed. We conclude that the activation of a cellular response is complex and affected by multiple signaling pathways.

Original languageEnglish
Pages (from-to)14192-14197
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume101
Issue number39
DOIs
Publication statusPublished - Sep 28 2004

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Hemocytes
Drosophila
Blood Cells
Genes
Cell Count
Wasps
Receptor Protein-Tyrosine Kinases
Mitogen-Activated Protein Kinases
Transgenes
Cellular Immunity
Larva
Parasites
Phosphotransferases
Phenotype

ASJC Scopus subject areas

  • Genetics
  • General

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A directed screen for genes involved in Drosophila blood cell activation. / Zettervall, Carl Johan; Anderl, Ines; Williams, Michael J.; Palmer, Ruth; Kurucz, E.; Andó, I.; Hultmark, Dan.

In: Proceedings of the National Academy of Sciences of the United States of America, Vol. 101, No. 39, 28.09.2004, p. 14192-14197.

Research output: Contribution to journalArticle

Zettervall, Carl Johan ; Anderl, Ines ; Williams, Michael J. ; Palmer, Ruth ; Kurucz, E. ; Andó, I. ; Hultmark, Dan. / A directed screen for genes involved in Drosophila blood cell activation. In: Proceedings of the National Academy of Sciences of the United States of America. 2004 ; Vol. 101, No. 39. pp. 14192-14197.
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