Integrins Modulate Extracellular Matrix Organization to Control Cell Signaling during Hematopoiesis

Abstract

During hematopoiesis, progenitor cells receive and interpret a diverse array of regulatory signals from their environment. These signals control the maintenance of the progenitors and regulate the production of mature blood cells. Integrins are well known in vertebrates for their roles in hematopoiesis, particularly in assisting in the migration to, as well as the physical attachment of, progenitors to the niche. However, whether and how integrins are also involved in the signaling mechanisms that control hematopoiesis remains to be resolved. Here, we show that integrins play a key role during fly hematopoiesis in regulating cell signals that control the behavior of hematopoietic progenitors. Integrins can regulate hematopoiesis directly, via focal adhesion kinase (FAK) signaling, and indirectly, by directing extracellular matrix (ECM) assembly and/or maintenance. ECM organization and density controls blood progenitor behavior by modulating multiple signaling pathways, including bone morphogenetic protein (BMP) and Hedgehog (Hh). Furthermore, we show that integrinsand the ECM are reduced following infection, which may assist in activating the immune response. Our results provide mechanistic insight into how integrins can shape the signaling environment around hematopoietic progenitors.