title: Nemo-like kinase-myocyte enhancer factor 2A signaling regulates anterior formation in Xenopus development.
abstract: The development of anterior neural structure in Xenopus laevis requires the inhibition of bone morphogenic protein 4 and Wnt signaling. We previously reported that Nemo-like kinase (NLK) negatively regulates Wnt signaling via the phosphorylation of T-cell factor/lymphoid enhancer factor. However, the molecular events occurring downstream of NLK pathways in early neural development remain unclear. In the present study, we identified the transcription factor myocyte enhancer factor 2A (MEF2A) as a novel substrate for NLK. NLK regulates the function of Xenopus MEF2A (xMEF2A) via phosphorylation, and this modification can be inhibited by the depletion of endogenous NLK. In Xenopus embryos, the depletion of either NLK or MEF2A results in a severe defect in anterior development. The endogenous expression of anterior markers was blocked by the depletion of endogenous Xenopus NLK (xNLK) or xMEF2A but, notably, not by the depletion of other xMEF2 family proteins, xMEF2C and xMEF2D. Defects in head formation or the expression of the anterior marker genes caused by the depletion of endogenous xMEF2A could be eliminated by the expression of wild-type xMEF2A, but not xMEF2A containing mutated xNLK phosphorylation sites. Furthermore, the expression of xNLK-induced anterior markers was efficiently blocked by the depletion of endogenous xMEF2A in animal pole explants. These results show that NLK specifically regulates the MEF2A activity required for anterior formation in Xenopus development.
authors.affiliation: Department of Molecular Cell Biology, Medical Research Institute, Tokyo Medical and Dental University, Chiyoda, Tokyo 101-0062, Japan.
authors.forename: Kiyotoshi
authors.initials: K
authors.lastname: Satoh
authors.forename: Junji
authors.initials: J
authors.lastname: Ohnishi
authors.forename: Atsushi
authors.initials: A
authors.lastname: Sato
authors.forename: Michio
authors.initials: M
authors.lastname: Takeyama
authors.forename: Shun-ichiro
authors.initials: S
authors.lastname: Iemura
authors.forename: Tohru
authors.initials: T
authors.lastname: Natsume
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Shibuya
mesh_terms: D000818:Animals; D019521:Body Patterning; D002460:Cell Line; D004625:Embryo, Nonmammalian / Q000201:enzymology; D018507:Gene Expression Regulation, Developmental; D006801:Humans; D064326:MEF2 Transcription Factors; D020928:Mitogen-Activated Protein Kinases / Q000235:genetics / Q000378:metabolism*; D018006:Myogenic Regulatory Factors / Q000235:genetics / Q000378:metabolism*; D009420:Nervous System / Q000196:embryology / Q000201:enzymology; D010766:Phosphorylation; D011485:Protein Binding; D020033:Protein Isoforms / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction; D014981:Xenopus / Q000196:embryology* / Q000235:genetics; D029867:Xenopus Proteins