Notch-regulated hematopoiesis in Drosophila: Parallels and contrasts with vertebrate blood development.

Drosophila melanogaster offers a genetically tractable model for dissecting the molecular logic of blood cell development. With a simple repertoire of blood cell types, Drosophila hematopoiesis relies on a conserved set of developmental pathways, among which Notch signaling emerges as a central regulator. In this review, we examine how Notch governs successive steps of blood cell development, including the initial specification of hematopoietic progenitors from the cardiogenic mesoderm, niche-dependent progenitor maintenance in the larval lymph gland, and fate decisions that include crystal cell specification, maturation, and transdifferentiation from plasmatocytes. We further address how Notch output is shaped by intracellular trafficking through the endolysosomal pathway, and how metabolic and environmental inputs are integrated to fine-tune lineage specification. Finally, we discuss how attenuation of Notch signaling in progenitors is required to permit lamellocyte differentiation in response to immune challenge. Throughout, we draw comparisons with vertebrate hematopoiesis, identifying conserved regulatory logic in progenitor emergence, niche-mediated stem cell maintenance, and binary fate decisions, while noting species-specific differences that reflect the distinct complexity of each system. Together, these analyses position Notch as a multifunctional developmental regulator whose activity underlies both homeostatic and adaptive blood cell production, and whose dysregulation is linked to hematological malignancies in humans.