Fibroblast Growth Factor (FGF) regulates human neuroectoderm specification through ERK1/2-PARP-1 pathway
| Autor: | Su-Chun Zhang, Timothy M. LaVaute, Cindy Tzu-Ling Huang, Young Dong Yoo, Xiaoqing Zhang |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2011 |
| Předmět: |
MAPK/ERK pathway
endocrine system PAX6 Transcription Factor MAP Kinase Signaling System Cellular differentiation Poly (ADP-Ribose) Polymerase-1 Biology Fibroblast growth factor Article Nitriles Butadienes Humans Paired Box Transcription Factors Pyrroles Phosphorylation Eye Proteins Cells Cultured Embryonic Stem Cells Homeodomain Proteins Neural Plate Neuroectoderm Cell Differentiation Cell Biology Phenanthrenes Molecular biology Cell biology Culture Media Enzyme Activation Fibroblast Growth Factors Repressor Proteins Gene Expression Regulation embryonic structures Molecular Medicine PAX6 Signal transduction Poly(ADP-ribose) Polymerases Neural development Neural plate Developmental Biology |
| Popis: | 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. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|