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PMID:15958512

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Citation

Tao, H, Shimizu, M, Kusumoto, R, Ono, K, Noji, S and Ohuchi, H (2005) A dual role of FGF10 in proliferation and coordinated migration of epithelial leading edge cells during mouse eyelid development. Development 132:3217-30

Abstract

The development of the eyelid requires coordinated cellular processes of proliferation, cell shape changes, migration and cell death. Mutant mice deficient in the fibroblast growth factor 10 (Fgf10) gene exhibit open-eyelids at birth. To elucidate the roles of FGF10 during eyelid formation, we examined the expression pattern of Fgf10 during eyelid formation and the phenotype of Fgf10-null eyelids in detail. Fgf10 is expressed by mesenchymal cells just beneath the protruding epidermal cells of the nascent eyelid. However, Fgf10-null epithelial cells running though the eyelid groove do not exhibit typical cuboid shape or sufficient proliferation. Furthermore, peridermal clumps are not maintained on the eyelid leading edge, and epithelial extension does not occur. At the cellular level, the accumulation of actin fibers is not observed in the mutant epithelial leading edge. The expression of activin/inhibin betaB (ActbetaB/Inhbb) and transforming growth factor alpha (Tgfa), previously reported to be crucial for eyelid development, is down-regulated in the mutant leading edge, while the onset of sonic hedgehog (Shh) expression is delayed on the mutant eyelid margin. Explant cultures of mouse eyelid primordia shows that the open-eyelid phenotype of the mutant is reduced by exogenous FGF10 protein, and that the expression of ActbetaB and Tgfa is ectopically induced in the thickened eyelid epithelium by the FGF10 protein. These results indicate a dual role of FGF10 in mouse eyelid development, for both proliferation and coordinated migration of eyelid epithelial cells by reorganization of the cytoskeleton, through the regulation of activin, TGFalpha and SHH signaling.

Links

PubMed Online version:10.1242/dev.01892

Keywords

Actins/metabolism; Animals; Cell Movement/genetics; Cell Movement/physiology; Cell Proliferation; Epithelial Cells/metabolism; Eyelids/embryology; Fibroblast Growth Factor 10; Fibroblast Growth Factors/biosynthesis; Fibroblast Growth Factors/genetics; Fibroblast Growth Factors/physiology; Hedgehog Proteins; Keratinocytes/cytology; Keratinocytes/physiology; Mesoderm/metabolism; Mice; Mice, Inbred C57BL; Mice, Inbred CBA; Mice, Knockout; Pseudopodia/physiology; Trans-Activators/metabolism; Transforming Growth Factor alpha/biosynthesis; Transforming Growth Factor alpha/genetics

Significance

Annotations

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

MOUSE:FGF10

acts_upstream_of_or_within

GO:0010634: positive regulation of epithelial cell migration

ECO:0000315: mutant phenotype evidence used in manual assertion

MGI:MGI:1859647

P

Seeded From UniProt

complete

MOUSE:FGF10

acts_upstream_of_or_within

GO:0050679: positive regulation of epithelial cell proliferation

ECO:0000315: mutant phenotype evidence used in manual assertion

MGI:MGI:1859647

P

Seeded From UniProt

complete

MOUSE:VIME

located_in

GO:0031252: cell leading edge

ECO:0000314: direct assay evidence used in manual assertion

C

  • part_of:(CL:0000362)

Seeded From UniProt

complete

MOUSE:VIME

located_in

GO:0031252: cell leading edge

ECO:0000314: direct assay evidence used in manual assertion

C

  • part_of:(CL:0000066)

Seeded From UniProt

complete

MOUSE:TBG1

located_in

GO:0005813: centrosome

ECO:0000314: direct assay evidence used in manual assertion

C

  • part_of:(CL:0000066)

Seeded From UniProt

complete

MOUSE:TBG1

located_in

GO:0045177: apical part of cell

ECO:0000314: direct assay evidence used in manual assertion

C

  • part_of:(CL:0000066)

Seeded From UniProt

complete

MOUSE:TBG1

located_in

GO:0031252: cell leading edge

ECO:0000314: direct assay evidence used in manual assertion

C

  • part_of:(CL:0000066)

Seeded From UniProt

complete

MOUSE:FGF10

acts_upstream_of_or_within

GO:0031076: embryonic camera-type eye development

ECO:0000315: mutant phenotype evidence used in manual assertion

MGI:MGI:1859647

P

Seeded From UniProt

complete

MOUSE:FGF10

acts_upstream_of_or_within

GO:0032925: regulation of activin receptor signaling pathway

ECO:0000315: mutant phenotype evidence used in manual assertion

MGI:MGI:1859647

P

Seeded From UniProt

complete

MOUSE:FGF10

acts_upstream_of_or_within

GO:0010631: epithelial cell migration

ECO:0000315: mutant phenotype evidence used in manual assertion

MGI:MGI:1859647

P

Seeded From UniProt

complete

MOUSE:FGF10

acts_upstream_of_or_within

GO:0010468: regulation of gene expression

ECO:0000315: mutant phenotype evidence used in manual assertion

MGI:MGI:1859647

P

Seeded From UniProt

complete

MOUSE:FGF10

acts_upstream_of_or_within

GO:0008589: regulation of smoothened signaling pathway

ECO:0000315: mutant phenotype evidence used in manual assertion

MGI:MGI:1859647

P

Seeded From UniProt

complete

MOUSE:FGF10

acts_upstream_of_or_within

GO:0050673: epithelial cell proliferation

ECO:0000315: mutant phenotype evidence used in manual assertion

MGI:MGI:1859647

P

Seeded From UniProt

complete

MOUSE:VIME

part_of

GO:0031252: cell leading edge

ECO:0000314: direct assay evidence used in manual assertion

C

part_of:(CL:0000066)

Seeded From UniProt

complete

MOUSE:VIME

part_of

GO:0031252: cell leading edge

ECO:0000314: direct assay evidence used in manual assertion

C

part_of:(CL:0000362)

Seeded From UniProt

complete


See also

References

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