|An FGF4-FRS2alpha-Cdx2 axis in trophoblast stem cells induces Bmp4 to regulate proper growth of early mouse embryos.|
|PMID: 19890878 Owner: NLM Status: MEDLINE|
|A variety of stem cells are controlled by the actions of multiple growth factors in vitro. However, it remains largely unclear how growth factors control the proliferation and differentiation of stem cells in vivo. Here, we describe a novel paracrine mechanism for regulating a stem cell niche in early mammalian embryos, which involves communication between the inner cell mass (ICM) and the trophectoderm, from which embryonic stem (ES) cells and trophoblast stem (TS) cells can be derived, respectively. It is known that ES cells produce fibroblast growth factor (FGF)4 and that TS cells produce bone morphogenetic protein (Bmp)4. We provide evidence that FRS2alpha mediates activation of the extracellular signal-regulated progein kinase (ERK) pathway to enhance expression of transcription factor Cdx2 in TS cells in response to FGF4. Cdx2 in turn binds to an FGF4-responsive enhancer element of the promoter region of Bmp4, leading to production and secretion of Bmp4. Moreover, exogenous Bmp4 is able to rescue the defective growth of Frs2alpha-null ICM. These findings suggest an important role of Cdx2 for production of Bmp4 in TS cells to promote the proper growth of early mouse embryos.|
|Michiko Murohashi; Takahisa Nakamura; Satoshi Tanaka; Taeko Ichise; Nobuaki Yoshida; Tadashi Yamamoto; Masabumi Shibuya; Joseph Schlessinger; Noriko Gotoh|
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|Type: Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't|
|Title: Stem cells (Dayton, Ohio) Volume: 28 ISSN: 1549-4918 ISO Abbreviation: Stem Cells Publication Date: 2010 Jan|
|Created Date: 2010-01-19 Completed Date: 2010-03-01 Revised Date: -|
Medline Journal Info:
|Nlm Unique ID: 9304532 Medline TA: Stem Cells Country: United States|
|Languages: eng Pagination: 113-21 Citation Subset: IM|
|Division of Genetics, University of Tokyo, Tokyo 108-863, Japan.|
|APA/MLA Format Download EndNote Download BibTex|
5' Flanking Region
Blastocyst Inner Cell Mass / cytology, drug effects, metabolism*
Bone Morphogenetic Protein 4 / genetics, metabolism*
Carrier Proteins / metabolism
Cell Differentiation* / drug effects, genetics
Cell Proliferation* / drug effects
Embryonic Stem Cells / drug effects, metabolism*
Enhancer Elements, Genetic
Extracellular Signal-Regulated MAP Kinases / antagonists & inhibitors, metabolism
Fibroblast Growth Factor 4 / metabolism*
Gene Expression Regulation, Developmental
Homeodomain Proteins / metabolism*
Membrane Proteins / deficiency, genetics, metabolism*
Protein Kinase Inhibitors / pharmacology
RNA, Messenger / metabolism
Recombinant Proteins / metabolism
Transcription Factors / metabolism*
Trophoblasts / drug effects, metabolism*
|AR 051448/AR/NIAMS NIH HHS; AR 051886/AR/NIAMS NIH HHS|
|0/Bmp4 protein, mouse; 0/Bone Morphogenetic Protein 4; 0/Carrier Proteins; 0/Cdx2 protein, mouse; 0/FRS2alpha protein, mouse; 0/Fgf4 protein, mouse; 0/Fibroblast Growth Factor 4; 0/Homeodomain Proteins; 0/Membrane Proteins; 0/Protein Kinase Inhibitors; 0/RNA, Messenger; 0/Recombinant Proteins; 0/Transcription Factors; 148294-77-3/noggin protein; EC 18.104.22.168/Extracellular Signal-Regulated MAP Kinases|
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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