FGF signalling through RAS/MAPK and PI3K pathways regulates cell movement and gene expression in the chicken primitive streak without affecting E-cadherin expression

Persistent Link:
http://hdl.handle.net/10150/610371
Title:
FGF signalling through RAS/MAPK and PI3K pathways regulates cell movement and gene expression in the chicken primitive streak without affecting E-cadherin expression
Author:
Hardy, Katharine; Yatskievych, Tatiana; Konieczka, J. H.; Bobbs, Alexander; Antin, Parker
Affiliation:
Department of Cell Biology and Anatomy, University of Arizona, Medical Research Building, 1656 E. Mabel Street, Tucson, AZ 85724, USA; Department of Cellular and Molecular Biology, University of Arizona, 1007 E. Lowell Street Tucson, AZ 85721, USA; Program in Cancer Biology and Epigenomics, Children's Memorial Research Center, Northwestern University Feinberg School of Medicine, 2300 Children's Plaza, Box 222, Chicago, IL 60614, USA; Department of Molecular and Cellular Biology, Harvard University, Cambridge, MA 02138, USA
Issue Date:
2011
Publisher:
BioMed Central
Citation:
Hardy et al. BMC Developmental Biology 2011, 11:20 http://www.biomedcentral.com/1471-213X/11/20
Journal:
BMC Developmental Biology
Rights:
© 2011 Hardy et al; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0)
Collection Information:
This item is part of the UA Faculty Publications collection. For more information this item or other items in the UA Campus Repository, contact the University of Arizona Libraries at repository@u.library.arizona.edu.
Abstract:
BACKGROUND:FGF signalling regulates numerous aspects of early embryo development. During gastrulation in amniotes, epiblast cells undergo an epithelial to mesenchymal transition (EMT) in the primitive streak to form the mesoderm and endoderm. In mice lacking FGFR1, epiblast cells in the primitive streak fail to downregulate E-cadherin and undergo EMT, and cell migration is inhibited. This study investigated how FGF signalling regulates cell movement and gene expression in the primitive streak of chicken embryos.RESULTS:We find that pharmacological inhibition of FGFR activity blocks migration of cells through the primitive streak of chicken embryos without apparent alterations in the level or intracellular localization of E-cadherin. E-cadherin protein is localized to the periphery of epiblast, primitive streak and some mesodermal cells. FGFR inhibition leads to downregulation of a large number of regulatory genes in the preingression epiblast adjacent to the primitive streak, the primitive streak and the newly formed mesoderm. This includes members of the FGF, NOTCH, EPH, PDGF, and canonical and non-canonical WNT pathways, negative modulators of these pathways, and a large number of transcriptional regulatory genes. SNAI2 expression in the primitive streak and mesoderm is not altered by FGFR inhibition, but is downregulated only in the preingression epiblast region with no significant effect on E-cadherin. Furthermore, over expression of SNAIL has no discernable effect on E-cadherin protein levels or localization in epiblast, primitive streak or mesodermal cells. FGFR activity modulates distinct downstream pathways including RAS/MAPK and PI3K/AKT. Pharmacological inhibition of MEK or AKT indicate that these downstream effectors control discrete and overlapping groups of genes during gastrulation. FGFR activity regulates components of several pathways known to be required for cell migration through the streak or in the mesoderm, including RHOA, the non-canonical WNT pathway, PDGF signalling and the cell adhesion protein N-cadherin.CONCLUSIONS:In chicken embryos, FGF signalling regulates cell movement through the primitive streak by mechanisms that appear to be independent of changes in E-cadherin expression or protein localization. The positive and negative effects on large groups of genes by pharmacological inhibition of FGF signalling, including major signalling pathways and transcription factor families, indicates that the FGF pathway is a focal point of regulation during gastrulation in chicken.
EISSN:
1471-213X
DOI:
10.1186/1471-213X-11-20
Version:
Final published version
Additional Links:
http://www.biomedcentral.com/1471-213X/11/20

Full metadata record

DC FieldValue Language
dc.contributor.authorHardy, Katharineen
dc.contributor.authorYatskievych, Tatianaen
dc.contributor.authorKonieczka, J. H.en
dc.contributor.authorBobbs, Alexanderen
dc.contributor.authorAntin, Parkeren
dc.date.accessioned2016-05-20T09:05:20Z-
dc.date.available2016-05-20T09:05:20Z-
dc.date.issued2011en
dc.identifier.citationHardy et al. BMC Developmental Biology 2011, 11:20 http://www.biomedcentral.com/1471-213X/11/20en
dc.identifier.doi10.1186/1471-213X-11-20en
dc.identifier.urihttp://hdl.handle.net/10150/610371-
dc.description.abstractBACKGROUND:FGF signalling regulates numerous aspects of early embryo development. During gastrulation in amniotes, epiblast cells undergo an epithelial to mesenchymal transition (EMT) in the primitive streak to form the mesoderm and endoderm. In mice lacking FGFR1, epiblast cells in the primitive streak fail to downregulate E-cadherin and undergo EMT, and cell migration is inhibited. This study investigated how FGF signalling regulates cell movement and gene expression in the primitive streak of chicken embryos.RESULTS:We find that pharmacological inhibition of FGFR activity blocks migration of cells through the primitive streak of chicken embryos without apparent alterations in the level or intracellular localization of E-cadherin. E-cadherin protein is localized to the periphery of epiblast, primitive streak and some mesodermal cells. FGFR inhibition leads to downregulation of a large number of regulatory genes in the preingression epiblast adjacent to the primitive streak, the primitive streak and the newly formed mesoderm. This includes members of the FGF, NOTCH, EPH, PDGF, and canonical and non-canonical WNT pathways, negative modulators of these pathways, and a large number of transcriptional regulatory genes. SNAI2 expression in the primitive streak and mesoderm is not altered by FGFR inhibition, but is downregulated only in the preingression epiblast region with no significant effect on E-cadherin. Furthermore, over expression of SNAIL has no discernable effect on E-cadherin protein levels or localization in epiblast, primitive streak or mesodermal cells. FGFR activity modulates distinct downstream pathways including RAS/MAPK and PI3K/AKT. Pharmacological inhibition of MEK or AKT indicate that these downstream effectors control discrete and overlapping groups of genes during gastrulation. FGFR activity regulates components of several pathways known to be required for cell migration through the streak or in the mesoderm, including RHOA, the non-canonical WNT pathway, PDGF signalling and the cell adhesion protein N-cadherin.CONCLUSIONS:In chicken embryos, FGF signalling regulates cell movement through the primitive streak by mechanisms that appear to be independent of changes in E-cadherin expression or protein localization. The positive and negative effects on large groups of genes by pharmacological inhibition of FGF signalling, including major signalling pathways and transcription factor families, indicates that the FGF pathway is a focal point of regulation during gastrulation in chicken.en
dc.language.isoenen
dc.publisherBioMed Centralen
dc.relation.urlhttp://www.biomedcentral.com/1471-213X/11/20en
dc.rights© 2011 Hardy et al; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0)en
dc.titleFGF signalling through RAS/MAPK and PI3K pathways regulates cell movement and gene expression in the chicken primitive streak without affecting E-cadherin expressionen
dc.typeArticleen
dc.identifier.eissn1471-213Xen
dc.contributor.departmentDepartment of Cell Biology and Anatomy, University of Arizona, Medical Research Building, 1656 E. Mabel Street, Tucson, AZ 85724, USAen
dc.contributor.departmentDepartment of Cellular and Molecular Biology, University of Arizona, 1007 E. Lowell Street Tucson, AZ 85721, USAen
dc.contributor.departmentProgram in Cancer Biology and Epigenomics, Children's Memorial Research Center, Northwestern University Feinberg School of Medicine, 2300 Children's Plaza, Box 222, Chicago, IL 60614, USAen
dc.contributor.departmentDepartment of Molecular and Cellular Biology, Harvard University, Cambridge, MA 02138, USAen
dc.identifier.journalBMC Developmental Biologyen
dc.description.collectioninformationThis item is part of the UA Faculty Publications collection. For more information this item or other items in the UA Campus Repository, contact the University of Arizona Libraries at repository@u.library.arizona.edu.en
dc.eprint.versionFinal published versionen
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