Notch signaling and its integration with other signaling mechanisms.
An improved understanding of stem cell differentiation is critical for progress in regenerative medicine. It is an emerging view that a relatively small number of intracellular signaling mechanisms play particularly important roles in differentiation control. As one may expect, these pathways are highly evolutionarily conserved, used in many tissues and iteratively during differentiation of a particular tissue. The Notch signaling system is one pathway meeting these criteria. In many cases, Notch signaling keeps stem/progenitor cells undifferentiated, although it can in some cellular contexts be instructive for differentiation toward a particular fate. Here, we review our current understanding of how Notch controls cellular differentiation in various organs and how Notch integrates with other major signaling pathways, primarily focusing on Notch signaling in mammals. Given the importance of Notch in many stem cell fate decisions, the possibility of experimentally manipulating Notch signaling opens up new avenues to control stem cell differentiation.
Sahlgren
Cecilia
C
Department of Cell and Molecular Biology, Medical Nobel Institute, Karolinska Institute, Stockholm, Sweden.
Lendahl
Urban
U
D000818:Animals; D019485:Bone Morphogenetic Proteins / Q000502:physiology; D002454:Cell Differentiation / Q000235:genetics / Q000502:physiology; D015687:Cell Hypoxia / Q000235:genetics / Q000502:physiology; D005855:Germ Layers / Q000166:cytology / Q000502:physiology; D006801:Humans; D020935:MAP Kinase Signaling System / Q000502:physiology; D008954:Models, Biological; D019869:Phosphatidylinositol 3-Kinases / Q000502:physiology; D051057:Proto-Oncogene Proteins c-akt / Q000502:physiology; D051880:Receptors, Notch / Q000502:physiology*; D015398:Signal Transduction / Q000235:genetics / Q000502:physiology*; D013234:Stem Cells / Q000502:physiology; D016212:Transforming Growth Factor beta / Q000502:physiology; D051153:Wnt Proteins / Q000502:physiology; D018631:ras Proteins / Q000502:physiology
D019485:Bone Morphogenetic Proteins; D051880:Receptors, Notch; D016212:Transforming Growth Factor beta; D051153:Wnt Proteins; D019869:Phosphatidylinositol 3-Kinases; D051057:Proto-Oncogene Proteins c-akt; D018631:ras Proteins