Septate junction components control Drosophila hematopoiesis through the Hippo pathway.

Hematopoiesis requires coordinated cell signals to control the proliferation and differentiation of progenitor cells. In Drosophila, blood progenitors, called prohemocytes, which are located in a hematopoietic organ called the lymph gland, are regulated by the Salvador-Warts-Hippo pathway. In epithelial cells, the Hippo pathway integrates diverse biological inputs, such as cell polarity and cell-cell contacts, but Drosophila blood cells lack the conspicuous polarity of epithelial cells. Here, we show that the septate-junction components Cora and NrxIV promote Hippo signaling in the lymph gland. Depletion of septate-junction components in hemocytes produces similar phenotypes to those observed in Hippo pathway mutants, including increased differentiation of immune cells. Our analysis places septate-junction components as upstream regulators of the Hippo pathway where they recruit Merlin to the membrane. Finally, we show that interactions of septate-junction components with the Hippo pathway are a key functional component of the cellular immune response following infection.