Fibroblast Growth Factor Regulates Human Neuroectoderm Specification Through ERK1/2-PARP-1 Pathway
Overview
Reproductive Medicine
Affiliations
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.
MeCP2 dysfunction prevents proper BMP signaling and neural progenitor expansion in brain organoid.
Hong H, Yoon S, Park J, Lee J, Kim H, Nam H Ann Clin Transl Neurol. 2023; 10(7):1170-1185.
PMID: 37302988 PMC: 10351674. DOI: 10.1002/acn3.51799.
Nelson M, Hoff J, Zeese M, Corfas G Front Cell Dev Biol. 2021; 9:693595.
PMID: 34708032 PMC: 8542860. DOI: 10.3389/fcell.2021.693595.
Differentiation of Human Pluripotent Stem Cells Into Specific Neural Lineages.
Chang C, Ting H, Liu C, Su H, Chiou T, Harn H Cell Transplant. 2021; 30:9636897211017829.
PMID: 34665040 PMC: 8529300. DOI: 10.1177/09636897211017829.
Poly(ADP-Ribosyl) Code Functions.
Maluchenko N, Koshkina D, Feofanov A, Studitsky V, Kirpichnikov M Acta Naturae. 2021; 13(2):58-69.
PMID: 34377556 PMC: 8327145. DOI: 10.32607/actanaturae.11089.
Papadopoulos A, Chalmantzi V, Hyvonen M, Stellas D, Syrrou M, Fotsis T Data Brief. 2021; 35:106844.
PMID: 33644271 PMC: 7893420. DOI: 10.1016/j.dib.2021.106844.