title: Fibroblast growth factor regulates human neuroectoderm specification through ERK1/2-PARP-1 pathway.
abstract: Fibroblast growth factor (FGF) signaling and PAX6 transcription are required for neuroectoderm specification of human embryonic stem cells (hESCs). In this study, we asked how FGF signaling leads to PAX6 transcription and neuroectoderm specification from hESCs. Under a chemically defined medium, FGF inhibition blocked phosphorylation of extracellular signal-regulated kinase 1/2 (ERK 1/2) with a significant reduction of PAX6-expressing neuroepithelia, indicating that FGF regulates neural induction through ERK1/2 activation. Activation of FGF-ERK1/2 pathway was necessary for the activity of poly(ADP-ribose) polymerase-1 (PARP-1), a conserved nuclear protein catalyzing polymerization of ADP-ribose units. Pharmacological inhibition and genetic ablation of PARP-1 inhibited neural induction from hESCs, suggesting that FGF-ERK1/2 signal pathway regulates neuroectoderm specification through regulating PARP-1 activity. Furthermore, FGF-ERK1/2-PARP-1 cascade regulated the expression of PAX6, a transcription determinant of human neuroectoderm. Together, we propose that FGF regulates hESC neural specification through the ERK1/2-PARP-1 signaling pathway.
authors: Waisman Center, University of Wisconsin-Madison, Madison, Wisconsin 53705, USA.
authors: Young Dong
authors: YD
authors: Yoo
authors: Cindy T
authors: CT
authors: Huang
authors: Xiaoqing
authors: X
authors: Zhang
authors: Timothy M
authors: TM
authors: Lavaute
authors: Su-Chun
authors: SC
authors: Zhang
mesh_terms: D002070:Butadienes / Q000494:pharmacology; D002454:Cell Differentiation; D002478:Cells, Cultured; D003470:Culture Media / Q000378:metabolism; D053595:Embryonic Stem Cells / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D004789:Enzyme Activation; D005136:Eye Proteins / Q000235:genetics / Q000378:metabolism*; D005346:Fibroblast Growth Factors / Q000235:genetics / Q000378:metabolism*; D005786:Gene Expression Regulation; D018398:Homeodomain Proteins / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D020935:MAP Kinase Signaling System; D054258:Neural Plate / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism; D009570:Nitriles / Q000494:pharmacology; D000071841:PAX6 Transcription Factor; D051761:Paired Box Transcription Factors / Q000235:genetics / Q000378:metabolism*; D010616:Phenanthrenes / Q000494:pharmacology; D010766:Phosphorylation; D000071137:Poly (ADP-Ribose) Polymerase-1; D011065:Poly(ADP-ribose) Polymerases / Q000235:genetics / Q000378:metabolism; D011758:Pyrroles / Q000494:pharmacology; D012097:Repressor Proteins / Q000235:genetics / Q000378:metabolism*
chemical_list: D002070:Butadienes; D003470:Culture Media; D005136:Eye Proteins; D018398:Homeodomain Proteins; C434926:N-(oxo-5,6-dihydrophenanthridin-2-yl)-N,N-dimethylacetamide hydrochloride; D009570:Nitriles; D000071841:PAX6 Transcription Factor; C000605730:PAX6 protein, human; D051761:Paired Box Transcription Factors; D010616:Phenanthrenes; D011758:Pyrroles; D012097:Repressor Proteins; C105686:SU 5402; C113580:U 0126; D005346:Fibroblast Growth Factors; C499320:PARP1 protein, human; D000071137:Poly (ADP-Ribose) Polymerase-1; D011065:Poly(ADP-ribose) Polymerases