title: Complex regulation of HSC emergence by the Notch signaling pathway.
abstract: Hematopoietic stem cells are formed during embryonic development, and serve as the foundation of the definitive blood program for life. Notch signaling has been well established as an essential direct contributor to HSC specification. However, several recent studies have indicated that the contribution of Notch signaling is complex. HSC specification requires multiple Notch signaling inputs, some received directly by hematopoietic precursors, and others that occur indirectly within neighboring somites. Of note, proinflammatory signals provided by primitive myeloid cells are needed for HSC specification via upregulation of the Notch pathway in hemogenic endothelium. In addition to multiple requirements for Notch activation, recent studies indicate that Notch signaling must subsequently be repressed to permit HSC emergence. Finally, Notch must then be reactivated to maintain HSC fate. In this review, we discuss the growing understanding of the dynamic contributions of Notch signaling to the establishment of hematopoiesis during development.
authors.affiliation: Department of Cellular and Molecular Medicine, University of California at San Diego, La Jolla, CA, USA.
authors.forename: Emerald
authors.initials: E
authors.lastname: Butko
authors.affiliation: Department of Cellular and Molecular Medicine, University of California at San Diego, La Jolla, CA, USA.
authors.forename: Claire
authors.initials: C
authors.lastname: Pouget
authors.affiliation: Department of Cellular and Molecular Medicine, University of California at San Diego, La Jolla, CA, USA. Electronic address: dtraver@ucsd.edu.
authors.forename: David
authors.initials: D
authors.lastname: Traver
mesh_terms: D000818:Animals; D001158:Arteries / Q000378:metabolism; D006412:Hematopoietic Stem Cells / Q000166:cytology* / Q000378:metabolism*; D006801:Humans; D007249:Inflammation / Q000473:pathology; D051880:Receptors, Notch / Q000378:metabolism*; D015398:Signal Transduction; D019170:Somites / Q000378:metabolism
chemical_list: D051880:Receptors, Notch
keywords: Hematopoiesis; Hematopoietic stem cell; Hemogenic endothelium; Notch signaling