The vascular niche controls Drosophila hematopoiesis via fibroblast growth factor signaling

Abstract

In adult mammals, hematopoiesis, the production of blood cells from hematopoietic stem and progenitor cells (HSPCs), is tightly regulated by extrinsic signals from the microenvironment called ‘niche’. Bone marrow HSPCs are heterogeneous and controlled by both endosteal and vascular niches. The Drosophila hematopoietic lymph gland is located along the cardiac tube which corresponds to the vascular system. In the lymph gland, the niche called Posterior Signaling Center controls only a subset of the heterogeneous hematopoietic progenitor population indicating that additional signals are necessary. Here we report that the vascular system acts as a second niche to control lymph gland homeostasis. The FGF ligand Branchless produced by vascular cells activates the FGF pathway in hematopoietic progenitors. By regulating intracellular calcium levels, FGF signaling maintains progenitor pools and prevents blood cell differentiation. This study reveals that two niches contribute to the control ofDrosophila blood cell homeostasis through their differential regulation of progenitors.

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

“…Sar1 regulates the formation of coat protein complex II (COPII), which is involved in transporting the newly synthesized proteins from the endoplasmic reticulum to the Golgi [ 56 – 58 ]. Downregulating sar1 , thus, leads to the intracellular accumulation of proteins that are otherwise meant to be released extracellularly [ 59 , 60 ]. Downregulation of sar1 function by Kn 13A11 -Gal4 following the scheme ( S6A Fig ) resulted in a drastic increase in differentiation and overall size of the lymph gland ( S6B–S6C′ Fig , and quantitated in S6E–S6G Fig ).…”

“…The multi-lobed lymph gland that spans from thoracic to abdominal segment with its stockpile of progenitors at different developmental stages provides us with a unique opportunity to unravel signals dedicated to their maintenance. The extrinsic, intrinsic, and systemic signals critical for maintaining the primary lobe progenitors have been extensively worked out [ 2 , 16 , 59 ]. In comparison, our understanding of the cells in the posterior lobe is limited.…”

Drosophila as a Model to Study Cellular Communication Between the Hematopoietic Niche and Blood Progenitors Under Homeostatic Conditions and in Response to an Immune Stress

“…Altogether, these data indicate that through the activation of Fibroblast Growth Factor (FGF) signaling, the vascular system prevents hematopoietic progenitors from massive differentiation, ensuring the proper balance between blood cell populations within the lymph gland. For the first time, this study provides evidence that the vascular system, which directly controls blood cell progenitors independently from the PSC, acts as a niche [Figure 2B and (84)]. In conclusion, two distinct niches, the PSC and the cardiac tube, control lymph gland homeostasis.…”

Macrophages and Their Organ Locations Shape Each Other in Development and Homeostasis – A Drosophila Perspective

“…Immune assaults and environmental challenges accelerate the differentiation of lymph gland progenitors and the release of differentiated plasmatocytes and other immune cells into circulation (Sorrentino et al, 2002;Crozatier et al, 2004;Márkus et al, 2005;Owusu-Ansah and Banerjee, 2009;Shim et al, 2013;Letourneau et al, 2016;Banerjee et al, 2019). Likewise, dysregulation of various major signaling pathways that usually tightly control normal lymph gland development can result in premature, or precocious, differentiation, including signaling by Notch (N), Hedgehog (Hh), Wingless (Wg), the Bone Morphogenetic Protein (BMP) Decapentaplegic (Dpp), receptor tyrosine kinases such as the PDGFR/VEGFR-related Receptor (PVR) and Fibroblast Growth Factor Receptor (FGFR), Hippo, JAK/STAT, NFκB-related Toll signaling and transcriptional regulators such as the zinc finger transcription factor Zfrp8 and the GATA factor Pannier (Qiu et al, 1998;Myrick and Dearolf, 2000;Lebestky et al, 2003;Crozatier et al, 2004;Mandal et al, 2007;Minakhina et al, 2007Minakhina et al, , 2011Sinenko et al, 2009;Pennetier et al, 2012;Dragojlovic-Munther and Martinez-Agosto, 2013;Ferguson and Martinez-Agosto, 2014;Milton et al, 2014;Destalminil-Letourneau et al, 2021). In contrast, under unchallenged conditions, the lymph gland disintegrates and releases all of its hemocytes at the beginning of metamorphosis (Grigorian et al, 2011).…”