Regulation of neural specification from human embryonic stem cells by BMP and FGF.
Inhibition of bone morphogenetic protein (BMP) signaling is required for vertebrate neural induction, and fibroblast growth factors (FGFs) may affect neural induction through phosphorylation at the linker region of Smad1, thus regulating BMP signaling. Here we show that human embryonic stem cells efficiently convert to neuroepithelial cells in the absence of BMP antagonists, or even when exposed to high concentrations of exogenous BMP4. Molecular and functional analyses revealed multiple levels of endogenous BMP signaling inhibition that may account for the efficient neural differentiation. Blocking FGF signaling inhibited neural induction, but did not alter the phosphorylation of the linker region of Smad1, suggesting that FGF enhances human neural specification independently of BMP signaling.
LaVaute
Timothy M
TM
Neuroscience Training Program, School of Medicine, University of Wisconsin-Madison, Madison, Wisconsin 53705, USA.
Yoo
Young Dong
YD
Pankratz
Matthew T
MT
Weick
Jason P
JP
Gerstner
Jason R
JR
Zhang
Su-Chun
SC
D055415:Bone Morphogenetic Protein 4 / Q000494:pharmacology*; D019485:Bone Morphogenetic Proteins / Q000037:antagonists & inhibitors* / Q000378:metabolism; D002352:Carrier Proteins / Q000494:pharmacology; D002454:Cell Differentiation / Q000187:drug effects / Q000502:physiology; D002478:Cells, Cultured; D053595:Embryonic Stem Cells / Q000166:cytology* / Q000187:drug effects* / Q000378:metabolism; D005136:Eye Proteins / Q000096:biosynthesis; D005346:Fibroblast Growth Factors / Q000037:antagonists & inhibitors / Q000378:metabolism*; D005455:Fluorescent Antibody Technique; D018398:Homeodomain Proteins / Q000096:biosynthesis; D006801:Humans; D007150:Immunohistochemistry; D009474:Neurons / Q000166:cytology* / Q000187:drug effects* / Q000378:metabolism; D050814:Octamer Transcription Factor-3 / Q000096:biosynthesis; D000071841:PAX6 Transcription Factor; D051761:Paired Box Transcription Factors / Q000096:biosynthesis; D010766:Phosphorylation; D012097:Repressor Proteins / Q000096:biosynthesis; D015398:Signal Transduction / Q000187:drug effects; D051898:Smad1 Protein / Q000037:antagonists & inhibitors / Q000378:metabolism; D000099176:Noggin Protein
D055415:Bone Morphogenetic Protein 4; D019485:Bone Morphogenetic Proteins; D002352:Carrier Proteins; D005136:Eye Proteins; D005346:Fibroblast Growth Factors; D018398:Homeodomain Proteins; D050814:Octamer Transcription Factor-3; D000071841:PAX6 Transcription Factor; D051761:Paired Box Transcription Factors; D012097:Repressor Proteins; D051898:Smad1 Protein; D000099176:Noggin Protein; C525809:BMP4 protein, human; C000605730:PAX6 protein, human; C494173:POU5F1 protein, human; C497399:SMAD1 protein, human