Abstract
Stem cells are regulated by signals from their microenvironment, or niche. During Drosophila hematopoiesis, a niche regulates prohemocytes to control hemocyte production. Immune challenges activate cell-signalling to initiate the cellular and innate immune response. Specifically, certain immune challenges stimulate the niche to produce signals that induce prohemocyte differentiation. However, the mechanisms that promote prohemocyte differentiation subsequent to immune challenges are poorly understood. Here we show that bacterial infection induces the cellular immune response by modulating occluding-junctions at the hematopoietic niche. Occluding-junctions form a permeability barrier that regulates the accessibility of prohemocytes to niche derived signals. The immune response triggered by infection causes barrier breakdown, altering the prohemocyte microenvironment to induce immune cell production. Moreover, genetically induced barrier ablation provides protection against infection by activating the immune response. Our results reveal a novel role for occluding-junctions in regulating niche-hematopoietic progenitor signalling and link this mechanism to immune cell production following infection.
Highlights
Stem cells are essential for animal development and allow the maintenance and regeneration of tissues
We found that ATPa and the Drosophila claudins, Sinuous and Kune-kune that are required for pleated septate junction organization and function show high levels of expression in the PSC (Figure 1—figure supplement 2g–l’)
Since PSC cells do not exhibit the conspicuous polarity of epithelial cells it seems that septate junctions are not localized to a particular domain
Summary
Stem cells are essential for animal development and allow the maintenance and regeneration of tissues. When stem cells divide the daughter cells can either self-renew to replenish the stem cell population or differentiate to give rise to a particular cell type (Fuchs and Chen, 2013). Stem cell differentiation and self-renewal are tightly regulated as producing too many stem cells can result in tumor formation while producing too many differentiated cells depletes the stem cell population (He et al, 2009). An important biological process where stem cell-niche interactions play a key regulatory role is the process of hematopoiesis, the production of new blood cells from hematopoietic progenitor cells, known as prohemocytes in Drosophila. Drosophila hematopoiesis produces blood cells, called hemocytes, that have specialized and essential functions in mediating fly immunity
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