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Yorkie and Scalloped signaling regulates progenitor maintenance and differentiation in Drosophila hematopoiesis

  • Author(s): Ferguson, Gabriel Benjamin
  • Advisor(s): Martinez-Agosto, Julian A
  • et al.
Abstract

Hematopoiesis is a highly complex developmental process that is remarkably conserved at the molecular level across higher order eukaryotes. An organ termed the lymph gland resides within the Drosophila larva which is the site of the majority of hematopoietic processes in the organism. The lymph gland contains a population of differentiating blood cells in addition to a pool of quiescent hematopoietic progenitors that are maintained by a small niche. While there has been a number of signaling pathways and mechanisms characterized in the regulation of lymph gland homeostasis, questions still remain unanswered in regards to the nature and requirement of progenitor cells and the mechanisms that promote differentiation in the lymph gland.

In this dissertation, we use genetic approaches to characterize the roles of the Hippo Pathway effectors Yorkie and Scalloped in regulating the maintenance and differentiation of hematopoietic progenitors through modulation of conserved signaling pathways. We show that differentiation of the crystal cell lineage of hemocytes is reliant on Yorkie and Scalloped dependent regulation of the Notch ligand Serrate in lineage specifying cells. Furthermore, Scalloped regulates organ size and differentiation of progenitors through modulation of the secreted factor PVF2 and its receptor PVR, respectively. Finally, we utilized an immune challenge model to interrogate the function of Yorkie and Scalloped in the cell fate decisions that are incurred during the cellular immune response induced by wasp parasitizaion. Using this immune challenge model, we demonstrated that wasp parasitization induces unique changes to Yorkie and Scalloped expression in the lymph gland. We also report that Serrate down-regulation in lineage specifying cells is critical for the cellular immune response, leading to a loss in crystal cell differentiation. Finally, we demonstrate a unique mechanism where-in Scalloped expression is enforced in the Posterior Signaling Center (PSC) of the lymph gland upon immune challenge by wasp parasitization as Scalloped function is required for maintenance of the PSC and differentiation of lamellocytes in the cellular immune response.

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