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Sakr, R.

Publications and source records attributed to Sakr, R..

3 recordsLinked to original sources

NimA promotes cell adhesion at the blood brain barrier of Drosophila nervous system

Glial cells are crucial for nervous system development and function, by clearing debris, protecting neurons, and ensuring neuronal survival. In Drosophila, glia also form the blood-brain barrier (BBB), which regulates neural stem cell proliferation and shields the nervous system while maintaining organism-wide communication. To uncover glial-specific roles, we compared their transcriptome with that of neurons and macrophages. Our study identifies NimA, an uncharacterized member of the Nimrod scavenger receptor family, as a glial-specific protein consistently expressed during development. Unlike other family members, i.e. NimC1 (macrophage-specific), Draper (shared by glia and macrophages), and NimC4/Simu (restricted to embryonic stages), NimA is not involved in phagocytosis. Instead, it regulates cell-cell interactions and adhesion, crucial for maintaining the tight septate junctions of the larval BBB. Loss of NimA compromises BBB integrity, delays development, reduces brain size and impairs neural stem cell proliferation. Altogether, the identification of a novel molecular player and more in general, of the glial-specific molecular landscape, are key to understand the contribution of glia to the construction and the function of the nervous system.

developmental biology↗

Novel cell- and stage-specific transcriptional signatures defining Drosophila neurons, glia and hemocytes

Cell types can be now defined at unprecedented resolution using high throughput assays. We analyzed the transcriptional signatures of Drosophila neurons, glia and hemocytes, as examples of cell types that are related by position (glia/neurons) or function (glia/hemocytes) or that are unrelated (neurons/hemocytes). The most related cells display the highest similarity level (neurons and glia), the least related ones, the lowest (neurons and hemocytes), however, cells can show plastic features. Glia are much more similar to neurons than to hemocytes in the embryo, but are equally similar to the two cell types in the larva, when hemocytes acquire more immune functions. Larval glia and hemocytes display common as well as specific immune features, such as the glia-specific NimA receptor, in agreement with the different environment faced by each cell types. Surprisingly, time represents a key identity parameter, as neurons, hemocytes and glia group more significantly by the stage than by the cell type and larval cells show upregulation of genes involved in chromatin organization and in DNA repair. This latter group of genes is linked to changes in gene expression levels and chromatin organization, revealing a function of these genes beyond DNA repair. Finally, the metabolic profiles reveal cell type-specific signatures and an overall shift from an embryonic, anabolic state to a larval, catabolic state.

developmental biology↗

Temporal specificity and heterogeneity of the fly immune cells' transcriptional landscape

Immune cells provide defense against the non-self, however recent data suggest roles well beyond innate immunity, in processes as diverse as development, metabolism and tumor progression. Nevertheless, the heterogeneity of these cells remains an open question. Using bulk RNA sequencing we find that the Drosophila immune cells (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. Through single cell RNA sequencing we identify fourteen hemocyte clusters present in unchallenged larvae and associated with distinct cellular processes e.g. proliferation, phagocytosis, metabolic homeostasis and humoral response. Finally, we characterize the changes occurring in the hemocyte clusters upon wasp infestation that triggers the differentiation of a novel cell type, the lamellocyte. This first molecular atlas provides precious insights and paves the way to study the biology of the Drosophila immune cells in physiological and pathological conditions.

developmental biology↗