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Drosophila (fruit flies) possess a highly effective innate immune system that provides defence against pathogens that include bacteria, fungi and parasites. Pathogens are neutralised by mechanisms that include phagocytosis, encapsulation and melanisation. Circulating cells called haemocytes are a key component of the innate immune system and include cells that resemble the granulocyte–macrophage lineages of mammals. The mechanisms that regulate Drosophila haematopoietic progenitor specification and differentiation are highly conserved, allowing Drosophila to be used as a useful model to understand transcriptional regulation of haematopoiesis. In this review I will summarise the mesodermal origin of Drosophila haemocyte precursors and describe parallels with mammalian haemangioblast precursors. I will discuss key signalling pathways and transcription factors that regulate differentiation of the three principal haemocyte cell types. There are significant parallels with the transcriptional circuitry that controls mammalian haematopoiesis, with transcription factors such as GATA factors, RUNX family members and STAT proteins influencing the specification and differentiation of Drosophila haemocytes. These transcription factors recruit co-repressor or co-activator complexes that alter chromatin structure to regulate gene expression. I will discuss how the Drosophila haematopoietic compartment has been used to explore function of ATP-dependent chromatin remodelling complexes and histone modifying complexes. As key regulators of haematopoiesis are conserved, the great genetic amenability of Drosophila offers a powerful system to dissect function of leukaemogenic fusion proteins such as RUNX1-ETO. In the final section of the review the use of genetic screens to identify novel RUNX1-ETO interacting factors will be discussed.
|Title of host publication||Transcriptional and Epigenetic Mechanisms Regulating Normal and Aberrant Blood Cell Development|
|Editors||Constanze Bonifer, Peter N. Cockerill|
|Number of pages||33|
|Publication status||Published - 2014|
|Name||Epigenetics and Human Health|
- Drosophila innate immunity
- Chromatin remodelling
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