Dual role for Jumu in the control of hematopoietic progenitors in the Drosophila lymph gland

Abstract

The Drosophila lymph gland is a hematopoietic organ in which the maintenance of hematopoietic progenitor cell fate relies on intrinsic factors and extensive interaction with cells within a microenvironment. The posterior signaling center (PSC) is required for maintaining the balance between progenitors and their differentiation into mature hemocytes. Moreover, some factors from the progenitors cell-autonomously control blood cell differentiation. Here, we show that Jumeau (Jumu), a member of the forkhead (Fkh) transcription factor family, controls hemocyte differentiation of lymph gland through multiple regulatory mechanisms. Jumu maintains the proper differentiation of prohemocytes by cell-autonomously regulating the expression of Col in medullary zone and by non-cell-autonomously preventing the generation of expanded PSC cells. Jumu can also cell-autonomously control the proliferation of PSC cells through positive regulation of dMyc expression. We also show that a deficiency of jumu throughout the lymph gland can induce the differentiation of lamellocytes via activating Toll signaling.DOI: http://dx.doi.org/10.7554/eLife.25094.001

Differential activation of JAK-STAT signaling in blood cell progenitors reveals functional compartmentalization of theDrosophilalymph gland

“…Immunostaining against the heparan sulfate proteoglycan (HSPG) Dally-like protein (Dlp), which was described as a PSC marker (Pennetier et al, 2012) (see also Figure S2A), revealed that it is expressed at high levels in the posterior lobes and at very low levels in the MZ of the anterior lobes ( Figure 2D). Consistent with the idea that its expression is activated by Col (Hao and Jin, 2017), Dlp displayed an antero-posterior gradient of expression similar to that of col ( Figure 2D), with particularly strong levels in the tertiary lobes. RNA in situ hybridization against Dystroglycan (Dg), which encodes a cell surface receptor for the extracellular matrix, showed that it is strongly expressed throughout the posterior lobes and at lower level in the MZ of the anterior lobes ( Figure 2E).…”

“…The general view is that these lobes essentially harbor progenitors as initially suggested by the higher expression of DE-cadherin and the lack of expression of mature blood cell markers (Jung et al, 2005). Yet only few studies on progenitor differentiation in the primary lobe report on phenotypes in the secondary lobes (Owusu-Ansah and , Dragojlovic-Munther and Martinez-Agosto, 2013, Khadilkar et al, 2017b, Hao and Jin, 2017, Zhang and Cadigan, 2017, Kulkarni et al, 2011, Benmimoun et al, 2015. These studies revealed that posterior lobes could also differentiate in genetic contexts where there is extensive premature differentiation in primary lobes, however a thorough analysis of the posterior LG lobes is lacking.…”

Comparative RNA-Seq analyses of Drosophila plasmatocytes reveal gene specific signatures in response to clean injury and septic injury

“…The three genes dome, hedgehog and Antennapedia, which positively regulate hematopoiesis in the lymph gland [48], were reduced in circulating plasmatocytes compared to whole larvae, with FCs of -5.3, -173.9 and -2903.3, respectively. Similarly, genes that promote pro-hemocyte maturation in the lymph gland, such as jumu, pyramus, thisbe and heartless were also down-regulated in hemocyte samples (with FCs of -2.2, -31.9, -1151.8 and -1655.5, respectively) [49,50]. The gene encoding the transcription factor collier (knot) that contributes to the lymph gland posterior signaling center [51] was not enriched in plasmatocytes.…”

Jumu is required for circulating hemocyte differentiation and phagocytosis in Drosophila

“…A previous study suggested that activation of the Toll pathway in hemocytes or fat body can induce lamellocyte formation [ 47 ]. Moreover, in a recent study, we demonstrated that loss of jumu in the entire lymph gland leads to the generation of lamellocytes through activation of Dif [ 34 ]. Thus, we next questioned whether the generation of lamellocytes in the circulating hemocytes of jumu GE27806 /Df(3R)Exel6157 was related to the Toll pathway.…”

“…Additionally, our previous studies have shown that Jumu is also expressed in hemocytes and fat body, involved in proper bacterial phagocytosis and resistance in adult flies, and overexpression of jumu both in the fat body and hemocytes induces melanotic nodules by activating Toll signaling [ 32 , 33 ]. Our recent study showed that Jumu plays crucial roles during Drosophila lymph gland hematopoiesis [ 34 ].…”