GONUTS has been updated to MW1.31 Most things seem to be working but be sure to report problems.

Have any questions? Please email us at ecoliwiki@gmail.com

PMID:18663143

From GONUTS
Jump to: navigation, search
Citation

Niessen, K, Fu, Y, Chang, L, Hoodless, PA, McFadden, D and Karsan, A (2008) Slug is a direct Notch target required for initiation of cardiac cushion cellularization. J. Cell Biol. 182:315-25

Abstract

Snail family proteins are key regulators of epithelial-mesenchymal transition, but their role in endothelial-to-mesenchymal transition (EMT) is less well studied. We show that Slug, a Snail family member, is expressed by a subset of endothelial cells as well as mesenchymal cells of the atrioventricular canal and outflow tract during cardiac cushion morphogenesis. Slug deficiency results in impaired cellularization of the cardiac cushion at embryonic day (E)-9.5 but is compensated by increased Snail expression at E10.5, which restores cardiac cushion EMT. We further demonstrate that Slug, but not Snail, is directly up-regulated by Notch in endothelial cells and that Slug expression is required for Notch-mediated repression of the vascular endothelial cadherin promoter and for promoting migration of transformed endothelial cells. In contrast, transforming growth factor beta (TGF-beta) induces Snail but not Slug. Interestingly, activation of Notch in the context of TGF-beta stimulation results in synergistic up-regulation of Snail in endothelial cells. Collectively, our data suggest that combined expression of Slug and Snail is required for EMT in cardiac cushion morphogenesis.

Links

PubMed PMC2483533 Online version:10.1083/jcb.200710067

Keywords

Antigens, CD/genetics; Antigens, CD/metabolism; Cadherins/genetics; Cadherins/metabolism; Cell Differentiation/genetics; Cell Line; Cell Movement/genetics; Endocardial Cushions/cytology; Endocardial Cushions/embryology; Endocardial Cushions/metabolism; Endothelial Cells/cytology; Endothelial Cells/metabolism; Gene Expression Regulation, Developmental/genetics; Heart/embryology; Humans; Mesoderm/cytology; Mesoderm/metabolism; Organogenesis/genetics; Promoter Regions, Genetic/genetics; Receptor, Notch1/genetics; Receptor, Notch1/metabolism; Stem Cells/cytology; Stem Cells/metabolism; Transcription Factors/genetics; Transcription Factors/metabolism; Transforming Growth Factor beta/genetics; Transforming Growth Factor beta/metabolism; Up-Regulation/genetics

Significance

Annotations

Gene product Qualifier GO Term Evidence Code with/from Aspect Extension Notes Status

HUMAN:SNAI2

enables

GO:0001227: DNA-binding transcription repressor activity, RNA polymerase II-specific

ECO:0000314: direct assay evidence used in manual assertion

F

  • occurs_at:(SO:0001952)

Seeded From UniProt

complete

MOUSE:PDGFB

involved_in

GO:0038033: positive regulation of endothelial cell chemotaxis by VEGF-activated vascular endothelial growth factor receptor signaling pathway

ECO:0000304: author statement supported by traceable reference used in manual assertion

P

Seeded From UniProt

complete

MOUSE:SUH

enables

GO:0001228: DNA-binding transcription activator activity, RNA polymerase II-specific

ECO:0000266: sequence orthology evidence used in manual assertion

UniProtKB:Q06330

F

Seeded From UniProt

complete

MOUSE:SNAI2

acts_upstream_of_or_within

GO:0006933: negative regulation of cell adhesion involved in substrate-bound cell migration

ECO:0000315: mutant phenotype evidence used in manual assertion

MGI:MGI:2447175

P

Seeded From UniProt

complete

MOUSE:SNAI2

acts_upstream_of_or_within

GO:0006929: substrate-dependent cell migration

ECO:0000315: mutant phenotype evidence used in manual assertion

MGI:MGI:2447175

P

  • results_in_movement_of:(CL:0000115)

Seeded From UniProt

complete

MOUSE:SNAI2

acts_upstream_of_or_within

GO:0003198: epithelial to mesenchymal transition involved in endocardial cushion formation

ECO:0000315: mutant phenotype evidence used in manual assertion

MGI:MGI:2447175

P

  • occurs_in:(EMAPA:16696)

Seeded From UniProt

complete

MOUSE:SNAI2

enables

GO:0001227: DNA-binding transcription repressor activity, RNA polymerase II-specific

ECO:0000314: direct assay evidence used in manual assertion

F

  • occurs_in:(CL:0000115)
  • has_input:(MGI:MGI:105057)

Seeded From UniProt

complete

MOUSE:SNAI2

involved_in

GO:0003273: cell migration involved in endocardial cushion formation

ECO:0000315: mutant phenotype evidence used in manual assertion

P

  • occurs_in:(UBERON:0002087)

Seeded From UniProt

complete

MOUSE:SNAI2

involved_in

GO:0003198: epithelial to mesenchymal transition involved in endocardial cushion formation

ECO:0000315: mutant phenotype evidence used in manual assertion

P

  • occurs_in:(UBERON:0002087)

Seeded From UniProt

complete

MOUSE:SNAI2

involved_in

GO:2001028: positive regulation of endothelial cell chemotaxis

ECO:0000305: curator inference used in manual assertion

GO:0003273

P

Seeded From UniProt

complete

MOUSE:SNAI2

involved_in

GO:0044319: wound healing, spreading of cells

ECO:0000304: author statement supported by traceable reference used in manual assertion

P

Seeded From UniProt

complete

MOUSE:SNAI2

involved_in

GO:0036120: cellular response to platelet-derived growth factor stimulus

ECO:0000304: author statement supported by traceable reference used in manual assertion

P

Seeded From UniProt

complete

HUMAN:SUH

involved_in

GO:0000122: negative regulation of transcription by RNA polymerase II

ECO:0000315: mutant phenotype evidence used in manual assertion

P

Seeded From UniProt

complete

HUMAN:SUH

involved_in

GO:0007219: Notch signaling pathway

ECO:0000315: mutant phenotype evidence used in manual assertion

P

Seeded From UniProt

complete

HUMAN:SUH

involved_in

GO:0045944: positive regulation of transcription by RNA polymerase II

ECO:0000315: mutant phenotype evidence used in manual assertion

P

Seeded From UniProt

complete

MOUSE:SNAI1

involved_in

GO:0003198: epithelial to mesenchymal transition involved in endocardial cushion formation

ECO:0000316: genetic interaction evidence used in manual assertion

UniProtKB:Q3UZ96

P

Seeded From UniProt

complete

HUMAN:SNAI2

involved_in

GO:0007219: Notch signaling pathway

ECO:0000315: mutant phenotype evidence used in manual assertion

P

Seeded From UniProt

complete

HUMAN:SNAI2

enables

GO:0001227: DNA-binding transcription repressor activity, RNA polymerase II-specific

ECO:0000314: direct assay evidence used in manual assertion

F

occurs_at:(SO:0001952)

Seeded From UniProt

complete

HUMAN:SNAI2

involved_in

GO:0000122: negative regulation of transcription by RNA polymerase II

ECO:0000315: mutant phenotype evidence used in manual assertion

P

Seeded From UniProt

complete

HUMAN:NOTC4

involved_in

GO:0007221: positive regulation of transcription of Notch receptor target

ECO:0000304: author statement supported by traceable reference used in manual assertion

P

Seeded From UniProt

complete


See also

References

See Help:References for how to manage references in GONUTS.