Control of blood cell homeostasis in Drosophila larvae by the posterior signalling centre

Abstract

Drosophila haemocytes (blood cells) originate from a specialized haematopoietic organ-the lymph gland. Larval haematopoietic progenitors (prohaemocytes) give rise to three types of circulating haemocytes: plasmatocytes, crystal cells and lamellocytes. Lamellocytes, which are devoted to encapsulation of large foreign bodies, only differentiate in response to specific immune threats, such as parasitization by wasps. Here we show that a small cluster of signalling cells, termed the PSC (posterior signalling centre), controls the balance between multipotent prohaemocytes and differentiating haemocytes, and is necessary for the massive differentiation of lamellocytes that follows parasitization. Communication between the PSC and haematopoietic progenitors strictly depends on the PSC-restricted expression of Collier, the Drosophila orthologue of mammalian early B-cell factor. PSC cells act, in a non-cell-autonomous manner, to maintain JAK/STAT signalling activity in prohaemocytes, preventing their premature differentiation. Serrate-mediated Notch signalling from the PSC is required to maintain normal levels of col transcription. The key role of the PSC in controlling blood cell homeostasis is reminiscent of interactions between haematopoietic progenitors and their micro-environment in vertebrates, thus further highlighting the interest of Drosophila as a model system for studying the evolution of haematopoiesis and cellular innate immunity.

Structural and functional characterization of pseudopodocyte, a shaggy immune cell produced by two Drosophila species of the obscura group

“…Thus, P1 and L1 antibodies seem to be specific of the melanogaster subgroup. In fact, none of the D. melanogaster hemocytes markers seemed to be exploitable with Drosophila species belonging to the obscura group: none of the other tested antibodies such as the a-PS4 antiserum specific to the lamellocyte-specific integrin a-chain, Talin specific to an integrin-linked kinase strongly expressed in lamellocytes (Krzemień et al, 2007), or 4B8, a lamellocyte-specific antibody recognizing filamin-240 (Rus et al, 2006) gave rise to any successful recognition of either D. affinis or D. obscura hemocytes. Therefore, it must be concluded that the presently available antibodies labeling D. melanogaster hemocytic proteins cannot allow heterospecific hybridization in species of the obscura group.…”

“…Then, PAT was removed and hematopoietic organs incubated over night at 4°C with primary antibodies diluted in PAT. The a-PS4 polyclonal rabbit antibody (Krzemień et al, 2007) was previously exhausted over night at 4°C in a PAT solution onto Drosophila embryos. Dilutions used were 1:200 for a-PS4 and 1:50 for Talin.…”

“…They are considered essential for encapsulation and were long described as a plasmatocyte-derived form Rizki, 1980, 1984). Many studies established that plasmatocytes and lamellocytes follow specific differentiation pathways (Lanot et al, 2001;Sorrentino et al, 2002Sorrentino et al, , 2004Meister, 2004;Crozatier et al, 2004;Krzemień et al, 2007). However, recent works on Drosophila hemocytes lineage showed that plasmatocytes could indeed differentiate into lamellocytes (Honti et al, 2010;Avet-Rochex et al, 2010;Stofanko et al, 2010).…”

Cell lineage tracing reveals the plasticity of the hemocyte lineages and of the hematopoietic compartments in Drosophila melanogaster

“…The primary lobes are separated into three functional areas: the medullary zone comprises prohemocytes, the cortical zone built up by plasmatocytes and crystal cells, and the posterior signaling center (PSC), formed by a few cells on the posterior tip of the primary lobes. The PSC halts the differentiation of the prohemocytes in the medullary zone (Mandal et al, 2007;Krzemień et al, 2007). The sessile population of hemocytes is located underneath the larval cuticle (Goto et al, 2003;Lanot et al, 2001;Zettervall et al, 2004), serving as a precursor pool for effector cells, plasmatocytes and lamellocytes in the course of the cell mediated immune response (Zettervall et al, 2004;Márkus et al, 2009).…”

Haematopoietic progenitor maintenance by EBF/Collier: beyond the Niche

“…Importantly, the PSC was proposed to act as a niche required for progenitor fate maintenance in the LG. 2,3 Notably it was shown that col mutant larvae, which lack a PSC, exhibit massive prohemocyte differentiation and that inhibiting Hh signalling pathway in the prohemocytes promote their differentiation. Moreover, several reports showed that modulating PSC size/activity affects the balance between progenitor and differentiated blood cells.…”