Septate junction components control hematopoiesis through the Hippo pathway.

Hematopoiesis requires coordinated cell signals to control the proliferation and differentiation of progenitor cells. In , 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 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.