Bone morphogenetic protein 4 stimulates neuronal differentiation of neuronal stem cells through the ERK pathway

Byoung San Moon, Ju Yong Yoon, Mi Yeon Kim, Sang Hun Lee, Thomas Choi, Kang-Yell Choi

Research output: Contribution to journalArticle

40 Citations (Scopus)

Abstract

Bone morphogenic protein 4 (BMP4), a member of the TGF-β superfamily, induced neural differentiation of neural stem cells (NSCs) grown in a medium containing basic fibroblast growth factor (bFGF). The Ras protein level and the activities of the downstream ERKs were increased by transfection of BMP4 or treatment with recombinant BMP4. The effects of BMP4, including activation of the Ras-ERK pathway and induction of the neuron marker β-tubulin type III (Tuj1), were blocked by co-treatment of the BMP4 antagonist, noggin. The roles of the Ras-ERK pathway in neuronal differentiation by BMP4 were revealed by measuring the effect of the ERK pathway inhibition by dominant negative Ras or PD98059, the MEK specific inhibitor. BMP4 is a transcriptional target of Wnt/β-catenin signaling, and both the mRNA and protein levels of BMP4 were increased by treatment of valproic acid (VPA), a chemical inhibitor of glycogen synthase kinase 3β (GSK3β) activating the Wnt/β-catenin pathway. The BMP4- mimicking effects of VPA, activation of the Ras-ERK pathway and induction of Tuj1, also were blocked by noggin. These results indicate the potential therapeutic usage of VPA as a replacement for BMP4.

Original languageEnglish
Pages (from-to)116-125
Number of pages10
JournalExperimental and Molecular Medicine
Volume41
Issue number2
DOIs
Publication statusPublished - 2009 Feb 28

Fingerprint

Bone Morphogenetic Protein 4
MAP Kinase Signaling System
Stem cells
Stem Cells
Bone
Bone and Bones
Proteins
Valproic Acid
Catenins
Chemical activation
Glycogen Synthase Kinase 3
ras Proteins
Wnt Signaling Pathway
Neural Stem Cells
Mitogen-Activated Protein Kinase Kinases
Fibroblast Growth Factor 2
Tubulin
Neurons
Transfection

All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Molecular Medicine
  • Molecular Biology
  • Clinical Biochemistry

Cite this

Moon, Byoung San ; Yoon, Ju Yong ; Kim, Mi Yeon ; Lee, Sang Hun ; Choi, Thomas ; Choi, Kang-Yell. / Bone morphogenetic protein 4 stimulates neuronal differentiation of neuronal stem cells through the ERK pathway. In: Experimental and Molecular Medicine. 2009 ; Vol. 41, No. 2. pp. 116-125.
@article{294c3295976142dba6fa9a9529c65d4e,
title = "Bone morphogenetic protein 4 stimulates neuronal differentiation of neuronal stem cells through the ERK pathway",
abstract = "Bone morphogenic protein 4 (BMP4), a member of the TGF-β superfamily, induced neural differentiation of neural stem cells (NSCs) grown in a medium containing basic fibroblast growth factor (bFGF). The Ras protein level and the activities of the downstream ERKs were increased by transfection of BMP4 or treatment with recombinant BMP4. The effects of BMP4, including activation of the Ras-ERK pathway and induction of the neuron marker β-tubulin type III (Tuj1), were blocked by co-treatment of the BMP4 antagonist, noggin. The roles of the Ras-ERK pathway in neuronal differentiation by BMP4 were revealed by measuring the effect of the ERK pathway inhibition by dominant negative Ras or PD98059, the MEK specific inhibitor. BMP4 is a transcriptional target of Wnt/β-catenin signaling, and both the mRNA and protein levels of BMP4 were increased by treatment of valproic acid (VPA), a chemical inhibitor of glycogen synthase kinase 3β (GSK3β) activating the Wnt/β-catenin pathway. The BMP4- mimicking effects of VPA, activation of the Ras-ERK pathway and induction of Tuj1, also were blocked by noggin. These results indicate the potential therapeutic usage of VPA as a replacement for BMP4.",
author = "Moon, {Byoung San} and Yoon, {Ju Yong} and Kim, {Mi Yeon} and Lee, {Sang Hun} and Thomas Choi and Kang-Yell Choi",
year = "2009",
month = "2",
day = "28",
doi = "10.3858/emm.2009.41.2.014",
language = "English",
volume = "41",
pages = "116--125",
journal = "Experimental and Molecular Medicine",
issn = "1226-3613",
publisher = "Korean Society of Med. Biochemistry and Mol. Biology",
number = "2",

}

Bone morphogenetic protein 4 stimulates neuronal differentiation of neuronal stem cells through the ERK pathway. / Moon, Byoung San; Yoon, Ju Yong; Kim, Mi Yeon; Lee, Sang Hun; Choi, Thomas; Choi, Kang-Yell.

In: Experimental and Molecular Medicine, Vol. 41, No. 2, 28.02.2009, p. 116-125.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Bone morphogenetic protein 4 stimulates neuronal differentiation of neuronal stem cells through the ERK pathway

AU - Moon, Byoung San

AU - Yoon, Ju Yong

AU - Kim, Mi Yeon

AU - Lee, Sang Hun

AU - Choi, Thomas

AU - Choi, Kang-Yell

PY - 2009/2/28

Y1 - 2009/2/28

N2 - Bone morphogenic protein 4 (BMP4), a member of the TGF-β superfamily, induced neural differentiation of neural stem cells (NSCs) grown in a medium containing basic fibroblast growth factor (bFGF). The Ras protein level and the activities of the downstream ERKs were increased by transfection of BMP4 or treatment with recombinant BMP4. The effects of BMP4, including activation of the Ras-ERK pathway and induction of the neuron marker β-tubulin type III (Tuj1), were blocked by co-treatment of the BMP4 antagonist, noggin. The roles of the Ras-ERK pathway in neuronal differentiation by BMP4 were revealed by measuring the effect of the ERK pathway inhibition by dominant negative Ras or PD98059, the MEK specific inhibitor. BMP4 is a transcriptional target of Wnt/β-catenin signaling, and both the mRNA and protein levels of BMP4 were increased by treatment of valproic acid (VPA), a chemical inhibitor of glycogen synthase kinase 3β (GSK3β) activating the Wnt/β-catenin pathway. The BMP4- mimicking effects of VPA, activation of the Ras-ERK pathway and induction of Tuj1, also were blocked by noggin. These results indicate the potential therapeutic usage of VPA as a replacement for BMP4.

AB - Bone morphogenic protein 4 (BMP4), a member of the TGF-β superfamily, induced neural differentiation of neural stem cells (NSCs) grown in a medium containing basic fibroblast growth factor (bFGF). The Ras protein level and the activities of the downstream ERKs were increased by transfection of BMP4 or treatment with recombinant BMP4. The effects of BMP4, including activation of the Ras-ERK pathway and induction of the neuron marker β-tubulin type III (Tuj1), were blocked by co-treatment of the BMP4 antagonist, noggin. The roles of the Ras-ERK pathway in neuronal differentiation by BMP4 were revealed by measuring the effect of the ERK pathway inhibition by dominant negative Ras or PD98059, the MEK specific inhibitor. BMP4 is a transcriptional target of Wnt/β-catenin signaling, and both the mRNA and protein levels of BMP4 were increased by treatment of valproic acid (VPA), a chemical inhibitor of glycogen synthase kinase 3β (GSK3β) activating the Wnt/β-catenin pathway. The BMP4- mimicking effects of VPA, activation of the Ras-ERK pathway and induction of Tuj1, also were blocked by noggin. These results indicate the potential therapeutic usage of VPA as a replacement for BMP4.

UR - http://www.scopus.com/inward/record.url?scp=63849150054&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=63849150054&partnerID=8YFLogxK

U2 - 10.3858/emm.2009.41.2.014

DO - 10.3858/emm.2009.41.2.014

M3 - Article

C2 - 19287192

AN - SCOPUS:63849150054

VL - 41

SP - 116

EP - 125

JO - Experimental and Molecular Medicine

JF - Experimental and Molecular Medicine

SN - 1226-3613

IS - 2

ER -