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:21703454

From GONUTS
Jump to: navigation, search
Citation

Ezratty, EJ, Stokes, N, Chai, S, Shah, AS, Williams, SE and Fuchs, E (2011) A role for the primary cilium in Notch signaling and epidermal differentiation during skin development. Cell 145:1129-41

Abstract

Ciliogenesis precedes lineage-determining signaling in skin development. To understand why, we performed shRNA-mediated knockdown of seven intraflagellar transport proteins (IFTs) and conditional ablation of Ift-88 and Kif3a during embryogenesis. In both cultured keratinocytes and embryonic epidermis, all of these eliminated cilia, and many (not Kif3a) caused hyperproliferation. Surprisingly and independent of proliferation, ciliary mutants displayed defects in Notch signaling and commitment of progenitors to differentiate. Notch receptors and Notch-processing enzymes colocalized with cilia in wild-type epidermal cells. Moreover, differentiation defects in ciliary mutants were cell autonomous and rescued by activated Notch (NICD). By contrast, Shh signaling was neither operative nor required for epidermal ciliogenesis, Notch signaling, or differentiation. Rather, Shh signaling defects in ciliary mutants occurred later, arresting hair follicle morphogenesis in the skin. These findings unveil temporally and spatially distinct functions for primary cilia at the nexus of signaling, proliferation, and differentiation.

Links

PubMed PMC3135909 Online version:10.1016/j.cell.2011.05.030

Keywords

Animals; Carrier Proteins/genetics; Cell Differentiation; Cell Polarity; Cell Proliferation; Cilia/metabolism; Cytoskeletal Proteins/metabolism; Epidermis/cytology; Epidermis/embryology; Epidermis/metabolism; Gene Knockdown Techniques; Hair Follicle/cytology; Hedgehog Proteins/metabolism; Kinesis; Mice; Receptors, Notch/metabolism; Signal Transduction; Tumor Suppressor Proteins/metabolism

Significance

Annotations

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

MOUSE:NOTC2

located_in

GO:0005929: cilium

ECO:0000314: direct assay evidence used in manual assertion

C

  • part_of:(EMAPA:17528)

Seeded From UniProt

complete

MOUSE:KIF3A

acts_upstream_of_or_within

GO:0008544: epidermis development

ECO:0000315: mutant phenotype evidence used in manual assertion

MGI:MGI:1926500,MGI:MGI:2386464

P

  • results_in_development_of:(EMAPA:17528)

Seeded From UniProt

complete

MOUSE:KIF3A

acts_upstream_of_or_within

GO:0060271: cilium assembly

ECO:0000315: mutant phenotype evidence used in manual assertion

MGI:MGI:1926500,MGI:MGI:2386464

P

  • occurs_in:(CL:0000312)|occurs_in:(EMAPA:17528)

Seeded From UniProt

complete

MOUSE:PSN2

located_in

GO:0036064: ciliary basal body

ECO:0000314: direct assay evidence used in manual assertion

C

  • part_of:(EMAPA:17528)

Seeded From UniProt

complete

MOUSE:IFT88

acts_upstream_of_or_within

GO:0031122: cytoplasmic microtubule organization

ECO:0000315: mutant phenotype evidence used in manual assertion

P

  • occurs_in:(CL:0000312)

Seeded From UniProt

complete

MOUSE:IFT88

acts_upstream_of_or_within

GO:0007219: Notch signaling pathway

ECO:0000315: mutant phenotype evidence used in manual assertion

P

  • occurs_in:(CL:0000312)

Seeded From UniProt

complete

MOUSE:IFT88

acts_upstream_of_or_within

GO:0008544: epidermis development

ECO:0000315: mutant phenotype evidence used in manual assertion

MGI:MGI:1926500,MGI:MGI:3710185

P

  • results_in_development_of:(EMAPA:17528)

Seeded From UniProt

complete

MOUSE:IFT88

acts_upstream_of_or_within

GO:1905515: non-motile cilium assembly

ECO:0000315: mutant phenotype evidence used in manual assertion

P

  • occurs_in:(CL:0000312)

Seeded From UniProt

complete

MOUSE:IFT52

acts_upstream_of_or_within

GO:0050680: negative regulation of epithelial cell proliferation

ECO:0000315: mutant phenotype evidence used in manual assertion

P

Seeded From UniProt

complete

MOUSE:IFT52

acts_upstream_of_or_within

GO:1905515: non-motile cilium assembly

ECO:0000315: mutant phenotype evidence used in manual assertion

P

  • occurs_in:(CL:0000312)

Seeded From UniProt

complete

MOUSE:IF122

acts_upstream_of_or_within

GO:1905515: non-motile cilium assembly

ECO:0000315: mutant phenotype evidence used in manual assertion

P

  • occurs_in:(CL:0000312)

Seeded From UniProt

complete

MOUSE:IF172

acts_upstream_of_or_within

GO:0031122: cytoplasmic microtubule organization

ECO:0000315: mutant phenotype evidence used in manual assertion

P

  • occurs_in:(CL:0000312)

Seeded From UniProt

complete

MOUSE:IF172

acts_upstream_of_or_within

GO:0007219: Notch signaling pathway

ECO:0000315: mutant phenotype evidence used in manual assertion

P

  • occurs_in:(CL:0000312)

Seeded From UniProt

complete

MOUSE:IF172

acts_upstream_of_or_within

GO:0008544: epidermis development

ECO:0000315: mutant phenotype evidence used in manual assertion

P

  • results_in_development_of:(EMAPA:17528)

Seeded From UniProt

complete

MOUSE:IF172

acts_upstream_of_or_within

GO:0050680: negative regulation of epithelial cell proliferation

ECO:0000315: mutant phenotype evidence used in manual assertion

P

Seeded From UniProt

complete

MOUSE:IF172

acts_upstream_of_or_within

GO:1905515: non-motile cilium assembly

ECO:0000315: mutant phenotype evidence used in manual assertion

P

  • occurs_in:(CL:0000312)

Seeded From UniProt

complete

MOUSE:IFT74

acts_upstream_of_or_within

GO:0007219: Notch signaling pathway

ECO:0000315: mutant phenotype evidence used in manual assertion

P

  • occurs_in:(CL:0000312)

Seeded From UniProt

complete

MOUSE:IFT74

acts_upstream_of_or_within

GO:0003334: keratinocyte development

ECO:0000315: mutant phenotype evidence used in manual assertion

P

  • results_in_development_of:(CL:0000312)

Seeded From UniProt

complete

MOUSE:IFT74

acts_upstream_of_or_within

GO:0008544: epidermis development

ECO:0000315: mutant phenotype evidence used in manual assertion

P

  • results_in_development_of:(EMAPA:17528)

Seeded From UniProt

complete

MOUSE:IFT74

acts_upstream_of_or_within

GO:0050680: negative regulation of epithelial cell proliferation

ECO:0000315: mutant phenotype evidence used in manual assertion

P

Seeded From UniProt

complete

MOUSE:IFT74

acts_upstream_of_or_within

GO:1905515: non-motile cilium assembly

ECO:0000315: mutant phenotype evidence used in manual assertion

P

  • occurs_in:(EMAPA:17528)|occurs_in:(CL:0000312)

Seeded From UniProt

complete

MOUSE:IFT57

acts_upstream_of_or_within

GO:1905515: non-motile cilium assembly

ECO:0000315: mutant phenotype evidence used in manual assertion

P

  • occurs_in:(CL:0000312)

Seeded From UniProt

complete

MOUSE:IFT80

acts_upstream_of_or_within

GO:0050680: negative regulation of epithelial cell proliferation

ECO:0000315: mutant phenotype evidence used in manual assertion

P

Seeded From UniProt

complete

MOUSE:IFT80

acts_upstream_of_or_within

GO:1905515: non-motile cilium assembly

ECO:0000315: mutant phenotype evidence used in manual assertion

P

  • occurs_in:(CL:0000312)

Seeded From UniProt

complete

MOUSE:KIF3A

acts_upstream_of_or_within

GO:0050679: positive regulation of epithelial cell proliferation

ECO:0000315: mutant phenotype evidence used in manual assertion

MGI:MGI:1926500,MGI:MGI:2386464

P

Seeded From UniProt

complete

MOUSE:KIF3A

acts_upstream_of_or_within

GO:0060271: cilium assembly

ECO:0000315: mutant phenotype evidence used in manual assertion

MGI:MGI:1926500,MGI:MGI:2386464

P

occurs_in:(CL:0000312)|occurs_in:(EMAPA:17528)

Seeded From UniProt

complete

MOUSE:KIF3A

acts_upstream_of_or_within

GO:0008544: epidermis development

ECO:0000315: mutant phenotype evidence used in manual assertion

MGI:MGI:1926500,MGI:MGI:2386464

P

results_in_development_of:(EMAPA:17528)

Seeded From UniProt

complete

MOUSE:IF122

acts_upstream_of_or_within

GO:1905515: non-motile cilium assembly

ECO:0000315: mutant phenotype evidence used in manual assertion

P

occurs_in:(CL:0000312)

Seeded From UniProt

complete

MOUSE:IF122

acts_upstream_of_or_within

GO:0050680: negative regulation of epithelial cell proliferation

ECO:0000315: mutant phenotype evidence used in manual assertion

P

Seeded From UniProt

complete

MOUSE:IFT88

acts_upstream_of_or_within

GO:1905515: non-motile cilium assembly

ECO:0000315: mutant phenotype evidence used in manual assertion

P

occurs_in:(CL:0000312)

Seeded From UniProt

complete

MOUSE:IFT88

acts_upstream_of_or_within

GO:0050680: negative regulation of epithelial cell proliferation

ECO:0000315: mutant phenotype evidence used in manual assertion

P

Seeded From UniProt

complete

MOUSE:IFT88

acts_upstream_of_or_within

GO:0050680: negative regulation of epithelial cell proliferation

ECO:0000315: mutant phenotype evidence used in manual assertion

MGI:MGI:1926500,MGI:MGI:3710185

P

Seeded From UniProt

complete

MOUSE:IFT88

acts_upstream_of_or_within

GO:0031122: cytoplasmic microtubule organization

ECO:0000315: mutant phenotype evidence used in manual assertion

P

occurs_in:(CL:0000312)

Seeded From UniProt

complete

MOUSE:IFT88

acts_upstream_of_or_within

GO:0008544: epidermis development

ECO:0000315: mutant phenotype evidence used in manual assertion

MGI:MGI:1926500,MGI:MGI:3710185

P

results_in_development_of:(EMAPA:17528)

Seeded From UniProt

complete

MOUSE:IFT88

acts_upstream_of_or_within

GO:0007219: Notch signaling pathway

ECO:0000315: mutant phenotype evidence used in manual assertion

P

occurs_in:(CL:0000312)

Seeded From UniProt

complete

MOUSE:IFT57

acts_upstream_of_or_within

GO:1905515: non-motile cilium assembly

ECO:0000315: mutant phenotype evidence used in manual assertion

P

occurs_in:(CL:0000312)

Seeded From UniProt

complete

MOUSE:IFT57

acts_upstream_of_or_within

GO:0050680: negative regulation of epithelial cell proliferation

ECO:0000315: mutant phenotype evidence used in manual assertion

P

Seeded From UniProt

complete

MOUSE:PSN2

part_of

GO:0036064: ciliary basal body

ECO:0000314: direct assay evidence used in manual assertion

C

part_of:(EMAPA:17528)

Seeded From UniProt

complete

Notes

See also

References

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