The vascular niche controlsDrosophilahematopoiesis 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 of Drosophila blood cell homeostasis through their differential regulation of progenitors.

Paths and pathways that generate cell-type heterogeneity and developmental progression in hematopoiesis

“…Serrate/Notch), interzonal communication (e.g. Hedgehog), signals from the neighboring cardiac tube (Morin-Poulard et al 2016;Destalminil-Letourneau et al 2021), and systemic signals (e.g. olfactory and nutritional) (Lebestky et al 2003;Crozatier et al 2004;Mandal et al 2007;Shim et al 2013;Ferguson and Martinez-Agosto 2014).…”

GPI-anchored FGF directs cytoneme-mediated bidirectional signaling to self-regulate tissue-specific dispersion

“…Bnl has a single receptor, Btl, and its activation induces MAPK signaling. Despite apparent similar stimulation, genetic analyses have revealed multiple functions for Bnl, such as acting as a mitogen, morphogen, or chemoattractant in diverse contexts, including stem cells, trachea, neuron/glial, blood cells, and cancer ( 8 , 10 , 12 – 18 ). We discovered that while cytonemes control tissue-specific Bnl distribution and signaling, Bnl glypiation programs the spatiotemporal origin, distribution, and plasticity of cytoneme contacts, thereby self-regulating its tissue-specific dispersion and functions.…”

“…In this study, we investigated these mechanisms by examining the inter-organ Bnl dispersion from the wing-disc Bnl-source to the recipient ASP. Like most paracrine signals, Bnl is predicted to be a readily secreted diffusible protein that produces different mitogenic, morphogenic, and motogenic responses in diverse recipient cells, including in stem cells, trachea, neuron/glia, and blood cells, by activating its receptor, Btl 14,[17][18][19][20][21] .…”

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, 2007 , 2011 ; Sinenko 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 ).…”