To Be, or Notch to Be: Mediating Cell Fate from Embryogenesis to Lymphopoiesis

Notch signaling forms an evolutionarily conserved juxtacrine pathway crucial for cellular development. Initially identified in Drosophila wing morphogenesis, Notch signaling has since been demonstrated to play pivotal roles in governing mammalian cellular development in a large variety of cell types. Indeed, abolishing Notch constituents in mouse models result in embryonic lethality, demonstrating that Notch signaling is critical for development and differentiation. In this review, we focus on the crucial role of Notch signaling in governing embryogenesis and differentiation of multiple progenitor cell types. Using hematopoiesis as a diverse cellular model, we highlight the role of Notch in regulating the cell fate of common lymphoid progenitors. Additionally, the influence of Notch through microenvironment interplay with lymphoid cells and how dysregulation influences disease processes is explored. Furthermore, bi-directional and lateral Notch signaling between ligand expressing source cells and target cells are investigated, indicating potentially novel therapeutic options for treatment of Notch-mediated diseases. Finally, we discuss the role of cis-inhibition in regulating Notch signaling in mammalian development.

Automated summary

Notch signaling plays a critical role in cellular development, particularly in the embryogenesis and differentiation of various progenitor cell types. By regulating cell fate in hematopoiesis, Notch influences the fate of lymphoid cells. Investigating the bi-directional and lateral Notch signaling pathways may offer novel therapeutic options for Notch-mediated diseases.