NF-κB (nuclear factor kappa B) belongs to a family of transcription factors known to regulate a broad range of processes such as immune cell function, proliferation and cancer, neuroprotection, and long-term memory. Upcoming fields of NF-κB research include its role in stem cells and developmental processes. In the present review, we discuss one role of NF-κB in development in Drosophila, Xenopus, mice, and humans in accordance with the concept of evo-devo (evolutionary developmental biology). REL domain-containing proteins of the NF-κB family are evolutionarily conserved among these species. In addition, we summarize cellular phenotypes such as defective B- and T-cell compartments related to genetic NF-κB defects detected among different species. While NF-κB proteins are present in nearly all differentiated cell types, mouse and human embryonic stem cells do not contain NF-κB proteins, potentially due to miRNA-dependent inhibition. However, the mesodermal and neuroectodermal differentiation of mouse and human embryonic stem cells is hampered upon the repression of NF-κB. We further discuss NF-κB as a crucial regulator of differentiation in adult stem cells such as neural crest-derived and mesenchymal stem cells. In particular, c-REL seems to be important for neuronal differentiation and the neuroprotection of human adult stem cells, while RELA plays a crucial role in osteogenic and mesodermal differentiation.
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