Salmonella pathogenesis reveals that BMP signaling regulates blood cell homeostasis and immune responses in Drosophila

Abstract

Intercellular signaling by bone morphogenetic proteins (BMPs) regulates developmental decisions in virtually all animals. Here, we report that Decapentaplegic (Dpp; a Drosophila BMP family member) plays a role in blood cell homeostasis and immune responses by regulating a transcription factor cascade. The cascade begins with Dpp repression of Zfh1, continues with Zfh1 activation of Serpent (Srp; a GATA factor), and terminates with Srp activation of U-shaped (Ush) in hematopoietic cells. Hyperactivation of Zfh1, Srp, and Ush in dpp mutants leads to hyperplasia of plasmatocytes. Salmonella challenge revealed that in dpp mutants the misregulation of this cascade also prevents the generation of lamellocytes. These findings support the hypothesis that Ush participates in a switch between plasmatocyte and lamellocyte fate in a common precursor and further suggests a mechanism for how all blood cell types can arise from a single progenitor. These results also demonstrate that combining Drosophila and Salmonella genetics can provide novel opportunities for advancing our knowledge of hematopoiesis and innate immunity.Serpent ͉ GATA ͉ plasmatocyte ͉ lamellocyte ͉ Decapentaplegic

Upregulation of the Drosophila Friend of GATA Gene u-shaped by JAK/STAT Signaling Maintains Lymph Gland Prohemocyte Potency

“…Dpp blocks zinc finger homeodomain protein 1 expression, which is required for the expression of srp. As a result, dpp mutant larvae have elevated Ush levels and are refractory to Salmonellainduced lamellocyte differentiation (19). Together, these observations suggest that the ush hematopoietic CRM acts as a nexus between the Dpp and JAK/STAT pathways, and antagonism between these pathways modulates ush expression (Fig.…”

Characterization of the TGF-β1 signaling abnormalities in the Gata1low mouse model of myelofibrosis

“…In Drosophila, the decapentaplegic gene (Dpp), the equivalent of TGF-b1, inhibits the maturation of crystal cells, the blood cells corresponding to mammalian MKs by suppressing the expression of Serpent, the GATA transcription factor in flies. 42,43 The conserved nature of the biological functions of the TGF-b family 1 suggests that TGF-b1 may also suppress Gata1 expression in mammalian MKs. In support of this hypothesis, SB431542 treatment, but not vehicle treatment, restored Gata1 expression in hematopoietic cells, including MKs, from BM of Gata1 low mice.…”

Size control of the Drosophila hematopoietic niche by bone morphogenetic protein signaling reveals parallels with mammals

“…For this reason, we used col > GFP > tkv DN for most of our analysis. Of note, a previous study, based on a hypomorphic dpp allele (cis-regulatory mutant), showed that impaired BMP signaling in the entire embryo resulted in a bigger embryonic LG, a phenotype persisting into third instar, although without significant difference in the number of Antp-expressing niche cells or differentiating crystal cells (23). The discrepancy between our present results and this initial report could be explained by the use of different alleles and different timing and targeting of dpp removal in the PSC.…”