A genetic melanotic neoplasm of Drosophila melanogaster

Hanratty, William P.; Ryerse, Jan S.

doi:10.1016/0012-1606(81)90470-x

Cited by 72 publications

(77 citation statements)

References 25 publications

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“…The ability to transfer sorted cells, rather than whole tissues [e.g., lymph glands or pseudotumors (24)] and to trace their fate after transfer into single hosts should facilitate developmental studies of hemocyte subsets and pools. In particular, sequential in vivo transfers, as performed in mammals, could help characterize Drosophila hematopoietic stem͞precursor cells.…”

Section: Discussionmentioning

confidence: 99%

“…Stocks used in this study include y, w 67 (control), Tum-l [Janus kinase gain-of-function mutant (24)], and Toll 10B [Toll gain-of-function mutant (25)]. The Tum-l͞11707 line was generated by crossing the Tum-l line and the LacZ enhancer-trap line, 11707 (26).…”

Section: Methodsmentioning

confidence: 99%

“…1B for y, w 67 control animals and Janus kinase mutants (Tum-l). Tum-l animals bear a dominant gain-offunction mutation of the Janus kinase hopscotch, resulting in cell hyperproliferation and, in the appearance of an activated subset, lamellocytes in the hemolymph (10,24,27).…”

Section: Detecting Drosophila Hemocytes Through Intracellular Glutathmentioning

confidence: 99%

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Fluorescence-activated cell sorting (FACS) of Drosophila hemocytes reveals important functional similarities to mammalian leukocytes

Tirouvanziam

Davidson

Lipsick

et al. 2004

Proc. Natl. Acad. Sci. U.S.A.

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Drosophila is a powerful model for molecular studies of hematopoiesis and innate immunity. However, its use for functional cellular studies remains hampered by the lack of single-cell assays for hemocytes (blood cells). Here we introduce a generic method combining fluorescence-activated cell sorting and nonantibody probes that enables the selective gating of live Drosophila hemocytes from the lymph glands (larval hematopoietic organ) or hemolymph (blood equivalent). Gated live hemocytes are analyzed and sorted at will based on precise quantitation of fluorescence levels originating from metabolic indicators, lectins, reporters (GFP and ␤-galactosidase) and antibodies. With this approach, we discriminate and sort plasmatocytes, the major hemocyte subset, from lamellocytes, an activated subset present in gain-of-function mutants of the Janus kinase and Toll pathways. We also illustrate how important, evolutionarily conserved, blood-cell-regulatory molecules, such as calcium and glutathione, can be studied functionally within hemocytes. Finally, we report an in vivo transfer of sorted live hemocytes and their successful reanalysis on retrieval from single hosts. This generic and versatile fluorescence-activated cell sorting approach for hemocyte detection, analysis, and sorting, which is efficient down to one animal, should critically enhance in vivo and ex vivo hemocyte studies in Drosophila and other species, notably mosquitoes.

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Section: Discussionmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

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Fluorescence-activated cell sorting (FACS) of Drosophila hemocytes reveals important functional similarities to mammalian leukocytes

Tirouvanziam

Davidson

Lipsick

et al. 2004

Proc. Natl. Acad. Sci. U.S.A.

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“…) also result in the neoplasia of fly blood cells and their inappropriate differentiation (metaplasia) into lamellocytes (Hanratty and Ryerse, 1981;Luo et al, 1997). This combination of neoplasic and metaplasic effects results in the generation of large numbers of ectopic lamellocytes and the spontaneous formation of melanised tumours composed of tightly associated plasmatocytes and lamellocytes.…”

Section: T42mentioning

confidence: 99%

Gα73Β is a downstream effector of JAK/STAT signalling and a regulator of Rho1 inDrosophilahaematopoiesis

Bausek

Zeidler

2013

Journal of Cell Science

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JAK/STAT signalling regulates many essential developmental processes including cell proliferation and haematopoiesis, whereas its inappropriate activation is associated with the majority of myeloproliferative neoplasias and numerous cancers. Furthermore, high levels of JAK/STAT pathway signalling have also been associated with enhanced metastatic invasion by cancerous cells. Strikingly, gain-of-function mutations in the single Drosophila JAK homologue, Hopscotch, result in haemocyte neoplasia, inappropriate differentiation and the formation of melanised haemocyte-derived 'tumour' masses; phenotypes that are partly orthologous to human gain-of-function JAK2-associated pathologies. Here we show that Ga73B, a novel JAK/STAT pathway target gene, is necessary for JAK/STAT-mediated tumour formation in flies. In addition, although Ga73B does not affect haemocyte differentiation, it does regulate haemocyte morphology and motility under non-pathological conditions. We show that Ga73B is required for constitutive, but not injury-induced, activation of Rho1 and for the localisation of Rho1 into filopodia upon haemocyte activation. Consistent with these results, we also show that Rho1 interacts genetically with JAK/STAT signalling, and that wild-type levels of Rho1 are necessary for tumour formation. Our findings link JAK/STAT transcriptional outputs, Ga73B activity and Rho1-dependent cytoskeletal rearrangements and cell motility, therefore connecting a pathway associated with cancer with a marker indicative of invasiveness. As such, we suggest a mechanism by which JAK/STAT pathway signalling may promote metastasis.

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“…In addition, two dominant alleles, hopTuml-(5) and hopT42 (H.L., W. P. Hanratty, and C.R.D., unpublished data) have been identified. These dominant mutations cause several defects, including a fruit fly "leukemia," the overproliferation, premature differentiation, and aggregation of hemocytes, the formation of melanotic masses of hemocytes and gut tissue, and the reduced viability of the mutant stock (6).…”

mentioning

confidence: 99%