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PMID:23284756

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Citation

Krolewski, RC, Packard, A, Jang, W, Wildner, H and Schwob, JE (2012) Ascl1 (Mash1) knockout perturbs differentiation of nonneuronal cells in olfactory epithelium. PLoS ONE 7:e51737

Abstract

The embryonic olfactory epithelium (OE) generates only a very few olfactory sensory neurons when the basic helix-loop-helix transcription factor, ASCL1 (previously known as MASH1) is eliminated by gene mutation. We have closely examined the structure and composition of the OE of knockout mice and found that the absence of neurons dramatically affects the differentiation of multiple other epithelial cell types as well. The most prominent effect is observed within the two known populations of stem and progenitor cells of the epithelium. The emergence of horizontal basal cells, a multipotent progenitor population in the adult epithelium, is anomalous in the Ascl1 knockout mice. The differentiation of globose basal cells, another multipotent progenitor population in the adult OE, is also aberrant. All of the persisting globose basal cells are marked by SOX2 expression, suggesting a prominent role for SOX2 in progenitors upstream of Ascl1. However, NOTCH1-expressing basal cells are absent from the knockout; since NOTCH1 signaling normally acts to suppress Ascl1 via HES1 and drives sustentacular (Sus) cell differentiation during adult epithelial regeneration, its absence suggests reciprocity between neurogenesis and the differentiation of Sus cells. Indeed, the Sus cells of the mutant mice express a markedly lower level of HES1, strengthening that notion of reciprocity. Duct/gland development appears normal. Finally, the expression of cKIT by basal cells is also undetectable, except in those small patches where neurogenesis escapes the effects of Ascl1 knockout and neurons are born. Thus, persistent neurogenic failure distorts the differentiation of multiple other cell types in the olfactory epithelium.

Links

PubMed PMC3524087 Online version:10.1371/journal.pone.0051737

Keywords

Animals; Basic Helix-Loop-Helix Transcription Factors/metabolism; Basic Helix-Loop-Helix Transcription Factors/physiology; Cell Differentiation; Cells, Cultured; Female; Gene Expression Regulation, Developmental; Homeodomain Proteins/metabolism; Immunoenzyme Techniques; Male; Mice; Mice, Knockout; Neurogenesis; Olfactory Mucosa/cytology; Olfactory Mucosa/metabolism; Proto-Oncogene Proteins c-kit/metabolism; Receptor, Notch1/metabolism; SOXB1 Transcription Factors/metabolism; Stem Cells/cytology; Stem Cells/metabolism

Significance

Annotations

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

MOUSE:KI67

located_in

GO:0005634: nucleus

ECO:0000314: direct assay evidence used in manual assertion

C

Seeded From UniProt

complete

MOUSE:KIT

located_in

GO:0005911: cell-cell junction

ECO:0000314: direct assay evidence used in manual assertion

C

Seeded From UniProt

complete

MOUSE:K1C18

located_in

GO:0071944: cell periphery

ECO:0000314: direct assay evidence used in manual assertion

C

Seeded From UniProt

complete

MOUSE:NCAM1

located_in

GO:0005911: cell-cell junction

ECO:0000314: direct assay evidence used in manual assertion

C

Seeded From UniProt

complete

MOUSE:PCNA

located_in

GO:0005634: nucleus

ECO:0000314: direct assay evidence used in manual assertion

C

  • part_of:(EMAPA:17606)

Seeded From UniProt

complete

MOUSE:EZRI

located_in

GO:0005902: microvillus

ECO:0000314: direct assay evidence used in manual assertion

C

Seeded From UniProt

complete

MOUSE:HES1

located_in

GO:0005634: nucleus

ECO:0000314: direct assay evidence used in manual assertion

C

Seeded From UniProt

complete

MOUSE:SOX2

located_in

GO:0005634: nucleus

ECO:0000314: direct assay evidence used in manual assertion

C

Seeded From UniProt

complete

MOUSE:NOTC1

located_in

GO:0071944: cell periphery

ECO:0000314: direct assay evidence used in manual assertion

C

Seeded From UniProt

complete

MOUSE:ASCL1

acts_upstream_of_or_within

GO:0030856: regulation of epithelial cell differentiation

ECO:0000315: mutant phenotype evidence used in manual assertion

MGI:MGI:3639318

P

Seeded From UniProt

complete

MOUSE:K1C14

located_in

GO:0071944: cell periphery

ECO:0000314: direct assay evidence used in manual assertion

C

Seeded From UniProt

complete

MOUSE:TBB4A

located_in

GO:0005929: cilium

ECO:0000314: direct assay evidence used in manual assertion

C

  • part_of:(EMAPA:17607)

Seeded From UniProt

complete

MOUSE:TBB3

located_in

GO:0043025: neuronal cell body

ECO:0000314: direct assay evidence used in manual assertion

C

Seeded From UniProt

complete

MOUSE:REEP6

located_in

GO:0045177: apical part of cell

ECO:0000314: direct assay evidence used in manual assertion

C

Seeded From UniProt

complete

MOUSE:UCHL1

located_in

GO:0043025: neuronal cell body

ECO:0000314: direct assay evidence used in manual assertion

C

  • part_of:(EMAPA:17607)

Seeded From UniProt

complete

MOUSE:K1C18

part_of

GO:0071944: cell periphery

ECO:0000314: direct assay evidence used in manual assertion

C

Seeded From UniProt

complete

MOUSE:SOX2

part_of

GO:0005634: nucleus

ECO:0000314: direct assay evidence used in manual assertion

C

Seeded From UniProt

complete

MOUSE:UCHL1

part_of

GO:0043025: neuronal cell body

ECO:0000314: direct assay evidence used in manual assertion

C

part_of:(EMAPA:17607)

Seeded From UniProt

complete

MOUSE:KI67

part_of

GO:0005634: nucleus

ECO:0000314: direct assay evidence used in manual assertion

C

Seeded From UniProt

complete

Notes

See also

References

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