The docking protein FRS2α is an essential component of multiple fibroblast growth factor responses during early mouse development Journal Article

   

Authors:	Gotoh, N.; Manova, K.; Tanaka, S.; Murohashi, M.; Hadari, Y.; Lee, A.; Hamada, Y.; Hiroe, T.; Ito, M.; Kurihara, T.; Nakazato, H.; Shibuya, M.; Lax, I.; Lacy, E.; Schlessinger, J.
Article Title:	The docking protein FRS2α is an essential component of multiple fibroblast growth factor responses during early mouse development
Abstract:	The docking protein FRS2α is a major mediator of fibroblast growth factor (FGF) signaling. However, the physiological role of FRS2α in vivo remains unknown. In this report, we show that Frs2α-null mouse embryos have a defect in anterior-posterior (A-P) axis formation and are developmentally retarded, resulting in embryonic lethality by embryonic day 8. We demonstrate that FRS2α is essential for the maintenance of self-renewing trophoblast stem (TS) cells in response to FGF4 in the extraembryonic ectoderm (ExE) that gives rise to tissues of the placenta. By analyzing chimeric embryos, we found that FRS2α also plays a role in cell movement through the primitive streak during gastrulation. In addition, experiments are presented demonstrating that Bmp4 expression in TS cells is controlled by mitogen-activated protein kinase-dependent FGF4 stimulation. Moreover, both the expression of Bmp4 in ExE and activation of Smad1/5 in epiblasts are reduced in Frs2α-null embryos. These experiments underscore the critical role of FRS2α in mediating multiple processes during embryonic development and reveal a potential new link between FGF and Bmp4 signaling pathways in early embryogenesis. Copyright © 2005, American Society for Microbiology. All Rights Reserved.
Keywords:	signal transduction; mitogen activated protein kinase; controlled study; protein expression; unclassified drug; nonhuman; protein function; animal cell; mouse; animal tissue; cell viability; smad1 protein; smad5 protein; embryo; animal experiment; cell motion; cell renewal; enzyme activation; chimera; growth retardation; trophoblast; gastrulation; ectoderm; bone morphogenetic protein 4; anterior posterior axis; primitive streak; embryo death; docking protein; protein nodal; fibroblast growth factor 4; docking protein frs2alpha
Journal Title:	Molecular and Cellular Biology
Volume:	25
Issue:	10
ISSN:	0270-7306
Publisher:	American Society for Microbiology
Date Published:	2005-05-01
Start Page:	4105
End Page:	4116
Language:	English
DOI:	10.1128/mcb.25.10.4105-4116.2005
PROVIDER:	scopus
PMCID:	PMC1087717
PUBMED:	15870281
DOI/URL:	http://www.scopus.com/inward/record.url?eid=2-s2.0-20144372283&partnerID=40&md5=fd7ff7f1334532c463dec2f82d734cdd
Notes:	--- - "Cited By (since 1996): 44" - "Export Date: 24 October 2012" - "CODEN: MCEBD" - "Source: Scopus"

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