title: Knockdown of IKK1/2 promotes differentiation of mouse embryonic stem cells into neuroectoderm at the expense of mesoderm.
abstract: Activation of nuclear factor kappa B (NF-κB) is accomplished by a specific kinase complex (IKK-complex), phosphorylating inhibitors of NF-κB (IκB). In embryonic stem cells (ESCs), NF-κB signaling causes loss of pluripotency and promotes differentiation towards a mesodermal phenotype. Here we show that NF-κB signaling is involved in cell fate determination during retinoic acid (RA) mediated differentiation of ESCs. Knockdown of IKK1 and IKK2 promotes differentiation of ESCs into neuroectoderm at the expense of neural crest derived myofibroblasts. Our data indicate that RA is not only able to induce neuronal differentiation in vitro but also drives ESCs into a neural crest cell lineage represented by differentiation towards peripheral neurons and myofibroblasts. The NC is a transiently existing, highly multipotent embryonic cell population generating a wide range of different cell types. During embryonic development the NC gives rise to distinct precursor lineages along the anterior-posterior axis determining differentiation towards specific derivates. Retinoic acid (RA) signaling provides essential instructive cues for patterning the neuroectoderm along the anterior-posterior axis. The demonstration of RA as a sufficient instructive signal for the differentiation of pluripotent cells towards NC and the involvement of NF-κB during this process provides useful information for the generation of specific NC-lineages, which are valuable for studying NC development or disease modeling.
authors: Department of Cell Biology, University of Bielefeld, Universitätsstr 25, 33501 Bielefeld, Germany.
authors: Patrick
authors: P
authors: Lüningschrör
authors: Barbara
authors: B
authors: Kaltschmidt
authors: Christian
authors: C
authors: Kaltschmidt
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology; D002454:Cell Differentiation / Q000187:drug effects / Q000502:physiology*; D002460:Cell Line; D019070:Cell Lineage / Q000187:drug effects / Q000502:physiology; D004622:Embryo, Mammalian / Q000166:cytology / Q000201:enzymology; D047108:Embryonic Development / Q000187:drug effects / Q000502:physiology; D053595:Embryonic Stem Cells / Q000166:cytology / Q000201:enzymology*; D055785:Gene Knockdown Techniques; D006801:Humans; D051550:I-kappa B Kinase / Q000235:genetics / Q000378:metabolism*; D008648:Mesoderm / Q000166:cytology / Q000201:enzymology*; D058628:Myofibroblasts / Q000166:cytology / Q000201:enzymology; D016328:NF-kappa B / Q000235:genetics / Q000378:metabolism; D054258:Neural Plate / Q000166:cytology / Q000201:enzymology*; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology; D014212:Tretinoin / Q000494:pharmacology
chemical_list: D000970:Antineoplastic Agents; D016328:NF-kappa B; D014212:Tretinoin; C496564:Chuk protein, mouse; D051550:I-kappa B Kinase; C496562:Ikbkb protein, mouse