Gcm counteracts Toll-induced inflammation and impacts hemocyte number through cholinergic signaling.

Hemocytes, the myeloid-like immune cells of , fulfill a variety of functions that are not completely understood, ranging from phagocytosis to transduction of inflammatory signals. We here show that downregulating the hemocyte-specific Glial cell deficient/Glial cell missing (Glide/Gcm) transcription factor enhances the inflammatory response to the constitutive activation of the Toll pathway. This correlates with lower levels of glutathione S-transferase, suggesting an implication of Glide/Gcm in reactive oxygen species (ROS) signaling and calling for a widespread anti-inflammatory potential of Glide/Gcm.

An anti-inflammatory transcriptional cascade conserved from flies to humans.

Innate immunity is an ancestral process that can induce pro- and anti-inflammatory states. A major challenge is to characterize transcriptional cascades that modulate the response to inflammation. Since the Drosophila glial cells missing (Gcm) transcription factor has an anti-inflammatory role, we explored its regulation and evolutionary conservation.

Toward a Consensus in the Repertoire of Hemocytes Identified in .

The catalog of the immune cells was until recently limited to three major cell types, based on morphology, function and few molecular markers. Three recent single cell studies highlight the presence of several subgroups, revealing a large diversity in the molecular signature of the larval immune cells. Since these studies rely on somewhat different experimental and analytical approaches, we here compare the datasets and identify eight common, robust subgroups associated to distinct functions such as proliferation, immune response, phagocytosis or secretion.

Tailoring the immune response to the availability of nutrients.

The development and the maintenance of an efficient immune system represents a considerable metabolic investment for the organism. Ramond et al. have characterized a new molecular and cellular pathway, inhibiting the immune system in poor diet conditions in the Drosophila larva.

Temporal specificity and heterogeneity of Drosophila immune cells.

Immune cells provide defense against non-self and have recently been shown to also play key roles in diverse processes such as development, metabolism, and tumor progression. The heterogeneity of Drosophila immune cells (hemocytes) remains an open question. Using bulk RNA sequencing, we find that the hemocytes display distinct features in the embryo, a closed and rapidly developing system, compared to the larva, which is exposed to environmental and metabolic challenges.

The Repo Homeodomain Transcription Factor Suppresses Hematopoiesis in and Preserves the Glial Fate.

Despite their different origins, glia and hemocytes are related cell populations that provide an immune function. hemocytes patrol the body cavity and act as macrophages outside the nervous system, whereas glia originate from the neuroepithelium and provide the scavenger population of the nervous system. glia are hence the functional orthologs of vertebrate microglia, even though the latter are cells of immune origin that subsequently move into the brain during development.

Embryonic hematopoiesis modulates the inflammatory response and larval hematopoiesis in .

Recent lineage tracing analyses have significantly improved our understanding of immune system development and highlighted the importance of the different hematopoietic waves. The current challenge is to understand whether these waves interact and whether this affects the function of the immune system. Here we report a molecular pathway regulating the immune response and involving the communication between embryonic and larval hematopoietic waves in .

An evolutionary conserved interaction between the Gcm transcription factor and the SF1 nuclear receptor in the female reproductive system.

NR5A1 is essential for the development and for the function of steroid producing glands of the reproductive system. Moreover, its misregulation is associated with endometriosis, which is the first cause of infertility in women. Hr39, the Drosophila ortholog of NR5A1, is expressed and required in the secretory cells of the spermatheca, the female exocrine gland that ensures fertility by secreting substances that attract and capacitate the spermatozoids.

The Glide/Gcm fate determinant controls initiation of collective cell migration by regulating Frazzled.

Collective migration is a complex process that contributes to build precise tissue and organ architecture. Several molecules implicated in cell interactions also control collective migration, but their precise role and the finely tuned expression that orchestrates this complex developmental process are poorly understood. Here, we show that the timely and threshold expression of the Netrin receptor Frazzled triggers the initiation of glia migration in the developing wing.

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

Master genes are known to induce the differentiation of a multipotent cell into a specific cell type. These molecules are often transcription factors that switch on the regulatory cascade that triggers cell specification. Gcm was first described as the master gene of the glial fate in Drosophila as it induces the differentiation of neuroblasts into glia in the developing nervous system.

Functional Conservation of the Glide/Gcm Regulatory Network Controlling Glia, Hemocyte, and Tendon Cell Differentiation in Drosophila.

High-throughput screens allow us to understand how transcription factors trigger developmental processes, including cell specification. A major challenge is identification of their binding sites because feedback loops and homeostatic interactions may mask the direct impact of those factors in transcriptome analyses. Moreover, this approach dissects the downstream signaling cascades and facilitates identification of conserved transcriptional programs.

The early life of a fly glial cell.

Throughout evolution, glia have key regulatory roles in neural development and function. Typically, they control the response to developmental and/or pathological signals, thereby affecting neural proliferation, remodeling, survival, and regeneration. Such complex biology depends on the plastic features of glial cells, but also on the presence of different classes of glial cells, hence the importance of understanding the cellular and the molecular mechanisms underlying their development.

The Drosophila fragile X mental retardation protein participates in the piRNA pathway.

RNA metabolism controls multiple biological processes, and a specific class of small RNAs, called piRNAs, act as genome guardians by silencing the expression of transposons and repetitive sequences in the gonads. Defects in the piRNA pathway affect genome integrity and fertility. The possible implications in physiopathological mechanisms of human diseases have made the piRNA pathway the object of intense investigation, and recent work suggests that there is a role for this pathway in somatic processes including synaptic plasticity.

New insights in the clockwork mechanism regulating lineage specification: Lessons from the Drosophila nervous system.

Background: Powerful transcription factors called fate determinants induce robust differentiation programs in multipotent cells and trigger lineage specification. These factors guarantee the differentiation of specific tissues/organs/cells at the right place and the right moment to form a fully functional organism. Fate determinants are activated by temporal, positional, epigenetic, and post-transcriptional cues, hence integrating complex and dynamic developmental networks.

Interlocked loops trigger lineage specification and stable fates in the Drosophila nervous system.

Multipotent precursors are plastic cells that generate different, stable fates at the correct number, place and time, to allow tissue and organ formation. While fate determinants are known to trigger specific transcriptional programs, the molecular pathway driving the progression from multipotent precursors towards stable and specific identities remains poorly understood. Here we demonstrate that, in Drosophila neural precursors, the glial determinant glial cell missing (Gcm) acts as a 'time bomb' and triggers its own degradation once the glial programme is stably activated.

Lineage specification in the fly nervous system and evolutionary implications.

Over the last decades, it has become clear that glia are multifunctional and plastic cells endowed with key regulatory roles. They control the response to developmental and/or pathological signals, thereby affecting neural proliferation, remodeling, survival, and regeneration. It is, therefore, important to understand the biology of these cells and the molecular mechanisms controlling their development/activity.

Transcriptome-wide identification of A > I RNA editing sites by inosine specific cleavage.

Adenosine to inosine (A > I) RNA editing, which is catalyzed by the ADAR family of proteins, is one of the fundamental mechanisms by which transcriptomic diversity is generated. Indeed, a number of genome-wide analyses have shown that A > I editing is not limited to a few mRNAs, as originally thought, but occurs widely across the transcriptome, especially in the brain. Importantly, there is increasing evidence that A > I editing is essential for animal development and nervous system function.

Pinstripe: a suite of programs for integrating transcriptomic and proteomic datasets identifies novel proteins and improves differentiation of protein-coding and non-coding genes.

Motivation: Comparing transcriptomic data with proteomic data to identify protein-coding sequences is a long-standing challenge in molecular biology, one that is exacerbated by the increasing size of high-throughput datasets. To address this challenge, and thereby to improve the quality of genome annotation and understanding of genome biology, we have developed an integrated suite of programs, called Pinstripe. We demonstrate its application, utility and discovery power using transcriptomic and proteomic data from publicly available datasets.