The Posterior Signaling Center Is an Important Microenvironment for Homeostasis of the Drosophila Lymph Gland

Abstract

Hematopoiesis is a necessary process for development and immune defense in Drosophila from the embryonic period to adulthood. There are two main stages in this process: the first stage occurs in the head mesoderm during the embryonic stage, and the second occurs in a specialized hematopoietic organ along the dorsal vessel, the lymph gland, during the larval stage. The lymph gland consists of paired lobes, each of which has distinct regions: the cortical zone (CZ), which contains mature hemocytes; the medullary zone (MZ), which contains hematopoietic progenitors; and the posterior signaling center (PSC), which specifically expresses the early B-cell factor (EBF) transcription factor Collier (Col) and the HOX factor Antennapedia (Antp) to form a microenvironment similar to that of the mammalian bone marrow hematopoietic stem cell niche. The PSC plays a key role in regulating hematopoietic progenitor differentiation. Moreover, the PSC contributes to the cellular immune response to wasp parasitism triggered by elevated ROS levels. Two recent studies have revealed that hematopoietic progenitor maintenance is directly regulated by Col expressed in the MZ and is independent of the PSC, challenging the traditional model. In this review, we summarize the regulatory networks of PSC cell proliferation, the controversy regarding PSC-mediated regulation of hematopoietic progenitor differentiation, and the wasp egg infection response. In addition, we discuss why the PSC is an ideal model for investigating mammalian hematopoietic stem cell niches and leukemia.

Drosophila Innate Immunity Involves Multiple Signaling Pathways and Coordinated Communication Between Different Tissues

“…The PL-Amp subpopulation significantly expresses AMPs. Some markers of the PL-ImpL2 subpopulation indicate that this cluster creates a niche through which immune cell differentiation is regulated, similar to the posterior signaling center (PSC) of the lymph gland (the Drosophila hematopoietic organ during the larval stage), which is the hematopoietic niche (19,32,36,37). The LM-1 and LM-2 subpopulations of lamellocytes represent mature lamellocytes and hemocytes in the plasmatocyte/lamellocyte intermediate state, respectively.…”

“…As mentioned above, the Toll pathway in the niche of lymph glands contributes to cellular immunity through the promotion of lamellocyte differentiation and dispersion of the lymph gland during systemic infection (63). Rel is inhibited upon bacterial infection, which disrupts Hedgehog signaling and thus hematopoietic progenitor maintenance (36). Moreover, hematopoietic progenitors differentiate into plasmatocytes but not lamellocytes during the cellular immune response (143).…”

Ubx-Collier signaling cascade maintains blood progenitors in the posterior lobes of the Drosophila larval lymph gland

“…It comprises proliferating blood progenitors developing inside a bi-laterally symmetrical multi-lobed organ consisting of primary, secondary, tertiary, and rarely quaternary lobes [4][5][6]. The anterior/primary lobe consists of three defined zones, a niche (posterior signaling center; [7][8][9], medullary zone (that includes pre-progenitors and intermediate progenitors [10][11][12][13][14]), and the cortical zone housing differentiated hemocytes [10]. The cells in the cortical zone consist of plasmatocytes, crystal cells, and lamellocytes; the latter formed only upon immune challenge; [1,15].…”

Paths and Pathways that Generate Cell-Type Heterogeneity and Developmental Progression in Hematopoiesis

“…Additional highly expressed genes include: Pvf1 , Dad , Dif , and EGFR , several of which are known to play roles in PSC function (Mondal et al 2011; Pennetier et al 2012; Sinenko et al 2012; Louradour et al 2017). The nature of the PSC has been extensively investigated prior to this study and many of the biological pathways important for PSC maintenance and function have been identified (Krzemień et al 2007; Mandal et al 2007; Sinenko et al 2009; Morin-Poulard et al 2016; reviewed in Luo et al 2020). When detectable, their corresponding genes are enriched in the PSC including: TGF beta signaling pathway ( Dad , Smox , Ubi-p5E , Ubi-p63E ), signaling by Robo receptors ( Dg , Ubi-p5E , Ubi-p63E , dlp ), positive regulators of Wnt gradient formation ( Flo2 , Ssdp , Swim , dally , dlp , flw , hipk , skd , spen ), genes that assist in cytoneme production ( Act5C , AnxB11 , Egfr , Flo1 , Flo2 , dlp , skd , sqh ) (Bischoff et al 2013), and plasma membrane bounded cell projection morphogenesis (40 different genes).…”