title: ERK1/2 is a key regulator of Fndc5 and PGC1α expression during neural differentiation of mESCs.
abstract: Fibronectin type III domain containing 5 (Fndc5) has already been distinguished to be involved in neural differentiation. However, cellular events of Fndc5 function are still ambiguous in the nervous system. One approach to shed light on duty of this protein in the nervous system is to find its cross-talks with various signaling pathways with defined characteristics and roles. Identification of the underlying molecular mechanism which controls Fndc5 expression and switches its activity up and down enables us to find out the Fndc5 functional map in the nervous system and other human body systems. Retinoic acid (RA) is a bio-small molecule which exerts its role as a neural inducer in the neurodevelopmental process of neural tube. RA up-regulates the expression of various genes involved in neural differentiation process via two distinct pathways: the genomic and the non-genomic. Our previous study has revealed that RA induces Fndc5 expression during neural differentiation process. In this study we have evaluated our hypothesis about the non-genomic up regulation of Fndc5 expression by RA. Interestingly we have identified that there is an association between ERK signaling pathway and Fndc5 expression. Furthermore, inhibition of this pathway by PD0325901 dramatically reduced Fndc5 mRNA level, while activating the pathway up-regulated Fndc5 transcription. In addition, it has been proven that ERK1/2 modulation via RA has more significant controlling effect on Fndc5 promoter rather than bFGF. This led us to conclude that RA enhances Fndc5 expression through a non-genomic pathway via the ERK signaling pathway.
authors: Cell and Molecular Biology Division, Biology Department, School of Sciences, University of Isfahan, Isfahan, Iran.
authors: S S
authors: SS
authors: Hosseini Farahabadi
authors: Cell and Molecular Biology Division, Biology Department, School of Sciences, University of Isfahan, Isfahan, Iran; Department of Cellular Biotechnology at Cell Science Research Center, Royan Institute for Biotechnology, ACECR, Isfahan, Iran. Electronic address: kamranghaedi@royaninstitute.org.
authors: K
authors: K
authors: Ghaedi
authors: Department of Cellular Biotechnology at Cell Science Research Center, Royan Institute for Biotechnology, ACECR, Isfahan, Iran.
authors: F
authors: F
authors: Ghazvini Zadegan
authors: Department of Cellular Biotechnology at Cell Science Research Center, Royan Institute for Biotechnology, ACECR, Isfahan, Iran.
authors: K
authors: K
authors: Karbalaie
authors: Department of Cellular Biotechnology at Cell Science Research Center, Royan Institute for Biotechnology, ACECR, Isfahan, Iran.
authors: F
authors: F
authors: Rabiee
authors: Department of Cellular Biotechnology at Cell Science Research Center, Royan Institute for Biotechnology, ACECR, Isfahan, Iran.
authors: M
authors: M
authors: Nematollahi
authors: Department of Stem Cells and Developmental Biology at Cell Science Research Center, Royan Institute for Stem Cell Biology and Technology, ACECR, Tehran, Iran; Department of Developmental Biology, University of Science and Culture, ACECR, Tehran, Iran.
authors: H
authors: H
authors: Baharvand
authors: Department of Cellular Biotechnology at Cell Science Research Center, Royan Institute for Biotechnology, ACECR, Isfahan, Iran. Electronic address: mh_nasr@royaninstitute.org.
authors: M-H
authors: MH
authors: Nasr-Esfahani
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology; D001549:Benzamides / Q000494:pharmacology; D002454:Cell Differentiation / Q000187:drug effects / Q000502:physiology*; D019295:Computational Biology; D004159:Diphenylamine / Q000031:analogs & derivatives / Q000494:pharmacology; D053595:Embryonic Stem Cells / Q000187:drug effects / Q000502:physiology*; D005346:Fibroblast Growth Factors / Q000494:pharmacology; D005353:Fibronectins / Q000235:genetics / Q000378:metabolism*; D005786:Gene Expression Regulation / Q000502:physiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D048052:Mitogen-Activated Protein Kinase 3 / Q000378:metabolism*; D047493:PPAR alpha / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D013997:Time Factors; D014212:Tretinoin / Q000494:pharmacology
chemical_list: D000970:Antineoplastic Agents; D001549:Benzamides; C571428:FNDC5 protein, mouse; D005353:Fibronectins; D047493:PPAR alpha; D012333:RNA, Messenger; D014212:Tretinoin; D005346:Fibroblast Growth Factors; C506614:mirdametinib; D004159:Diphenylamine; D048052:Mitogen-Activated Protein Kinase 3
keywords: ERK1/2; Fndc5; bFGF; neural differentiation; signaling pathway