A novel role of the glial fate determinant glial cells missing in hematopoiesis

Abstract

Glial cell deficient/Glial cells missing (Glide/Gcm) transcription factor is expressed in all glial precursors of the Drosophila embryo. Gcm is necessary and sufficient to induce glial differentiation but also plays a role in other cell types, by interacting with specific factors. To find potential partners of Gcm which trigger these other pathways, we performed a yeast two-hybrid screen and identified dpias, a gene involved in post-embryonic hematopoiesis. dpias larvae show melanotic tumors due to excess of lamellocytes, a hemocyte lineage that is involved in non-self recognition. We here show that blocking Gcm activity also triggers melanotic tumors and that gcm interacts genetically with dpias. Moreover, the members of the Janus Kinase (JAK)/ Signal Transducer and Activator of Transcription (STAT) pathway, which are known for their role in the vertebrate and invertebrate immune system and are required for dpias-dependent tumor formation, act downstream of Gcm. Altogether, this study identifies an unpredicted role of Gcm, dictated by its cofactor dpias, allowing Gcm to act in a specific pathway. Together with the recent finding that glia act as scavengers during development and in pathological conditions, our data open new perspectives onto the cellular and molecular pathways involved in non-self recognition within and outside the nervous system.

The transcriptional diversity of 25 Drosophila cell lines

“…Like Kc167, S2R+ and the tumorous blood cell line mbn2 express Pxn, Hml, and He. In contrast, S2-DRSC expresses a high level of proPO-A1 (formerly Bc) and a detectable level of lz, both associated with crystal cells and not with plasmatocytes ( Jung et al 2005;Jacques et al 2009); it also expresses a very high level of the plasmatocyte marker Pxn along with ush, an inhibitor of crystal cell differentiation. Thus, S2-DRSC combines properties of plasmatocytes and crystal cells; our data do not permit us to determine whether individual cells express both plasmatocyte markers and crystal cell markers, but we think it likely that this line contains a mixture of cell types.…”

“…In Drosophila, three classes of hemocytes arise from a common precursor by divergent pathways: crystal cells plasmatocytes (and closely related macrophages) and lamellocytes. Kc cells (including the line Kc167), which have been previously reported to have hemocyte properties (Andres and Cherbas 1992), express the plasmatocyte marker Pxn as well as ush, whose expression inhibits crystal cell differentiation (Fossett et al 2001) and more general hemocyte markers, including Hml (Charroux and Royet 2009) and He (Lebestky et al 2000;Jung et al 2005;Jacques et al 2009). None of these genes are entirely specific for hemocytes, as illustrated by their expression in other cell lines and by tissue expression data from FlyAtlas (Chintapalli et al 2007), but taken together, they suggest a plasmatocyte identity for Kc167 cells.…”

The Gcm/Glide molecular and cellular pathway: New actors and new lineages

“…Finally, gcm is required in additional cell types, including postembryonic neuronal subpopulations (Yoshida et al, 2005;Chotard et al, 2005;Colonques et al, 2007;Soustelle and Giangrande, 2007a;Soustelle et al, 2007), tendons (Soustelle et al, 2004) and blood cells (Bernardoni et al, 1997;Alfonso and Jones, 2002;Bataillé et al, 2005;Jacques et al, 2009).…”

Revisiting the role of the Gcm transcription factor, from master regulator to Swiss army knife

“…42 The cytokines activate the JAK/STAT pathway, thus inducing plasmatocytes proliferation and differentiation into lamellocytes, [43][44][45][46] which then encapsulate the wasp egg. 40,47 Gcm was previously described as an inhibitor of the JAK/STAT pathway, 48 and the DamID screen indicates that Gcm targets the transcription factor Stat92E, the inhibitors Ptp61F and Socs36E and the cytokine Upd1.…”