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PMID:9864371

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Citation

Gallicano, GI, Kouklis, P, Bauer, C, Yin, M, Vasioukhin, V, Degenstein, L and Fuchs, E (1998) Desmoplakin is required early in development for assembly of desmosomes and cytoskeletal linkage. J. Cell Biol. 143:2009-22

Abstract

Desmosomes first assemble in the E3.5 mouse trophectoderm, concomitant with establishment of epithelial polarity and appearance of a blastocoel cavity. Throughout development, they increase in size and number and are especially abundant in epidermis and heart muscle. Desmosomes mediate cell-cell adhesion through desmosomal cadherins, which differ from classical cadherins in their attachments to intermediate filaments (IFs), rather than actin filaments. Of the proteins implicated in making this IF connection, only desmoplakin (DP) is both exclusive to and ubiquitous among desmosomes. To explore its function and importance to tissue integrity, we ablated the desmoplakin gene. Homozygous -/- mutant embryos proceeded through implantation, but did not survive beyond E6.5. Surprisingly, analysis of these embryos revealed a critical role for desmoplakin not only in anchoring IFs to desmosomes, but also in desmosome assembly and/or stabilization. This finding not only unveiled a new function for desmoplakin, but also provided the first opportunity to explore desmosome function during embryogenesis. While a blastocoel cavity formed and epithelial cell polarity was at least partially established in the DP (-/-) embryos, the paucity of desmosomal cell-cell junctions severely affected the modeling of tissue architecture and shaping of the early embryo.

Links

PubMed PMC2175222

Keywords

Animals; Cytoskeletal Proteins/physiology; Cytoskeleton/metabolism; Cytoskeleton/ultrastructure; Desmoplakins; Desmosomes/metabolism; Desmosomes/ultrastructure; Embryo Transfer; Embryonic and Fetal Development/physiology; Female; Genes, Lethal; Gestational Age; Mice; Mice, Inbred C57BL; Mice, Knockout

Significance

Annotations

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

MOUSE:DESP

acts_upstream_of_or_within

GO:0002934: desmosome organization

ECO:0000315: mutant phenotype evidence used in manual assertion

MGI:MGI:2182575

P

  • occurs_in:(EMAPA:25765)

Seeded From UniProt

complete

MOUSE:DESP

located_in

GO:0005911: cell-cell junction

ECO:0000314: direct assay evidence used in manual assertion

C

  • part_of:(EMAPA:16050)|part_of:(EMAPA:16053)|part_of:(EMAPA:16046)|part_of:(EMAPA:25765)

Seeded From UniProt

complete

MOUSE:DESP

acts_upstream_of_or_within

GO:0045104: intermediate filament cytoskeleton organization

ECO:0000315: mutant phenotype evidence used in manual assertion

MGI:MGI:2182575

P

  • occurs_in:(EMAPA:25765)

Seeded From UniProt

complete

MOUSE:DESP

acts_upstream_of_or_within

GO:0098609: cell-cell adhesion

ECO:0000315: mutant phenotype evidence used in manual assertion

MGI:MGI:2182575

P

Seeded From UniProt

complete

MOUSE:DSG2

located_in

GO:0030057: desmosome

ECO:0000314: direct assay evidence used in manual assertion

C

  • part_of:(EMAPA:25765)

Seeded From UniProt

complete

MOUSE:CADH1

located_in

GO:0005911: cell-cell junction

ECO:0000314: direct assay evidence used in manual assertion

C

  • part_of:(EMAPA:25765)|part_of:(EMAPA:25765)

Seeded From UniProt

complete

MOUSE:DSC2

located_in

GO:0030057: desmosome

ECO:0000314: direct assay evidence used in manual assertion

C

  • part_of:(EMAPA:25765)

Seeded From UniProt

complete

MOUSE:PLAK

located_in

GO:0030057: desmosome

ECO:0000314: direct assay evidence used in manual assertion

C

  • part_of:(EMAPA:25765)

Seeded From UniProt

complete

MOUSE:Q3TIY5

located_in

GO:0030057: desmosome

ECO:0000314: direct assay evidence used in manual assertion

C

  • part_of:(EMAPA:25765)

Seeded From UniProt

complete

MOUSE:Q9CQ73

located_in

GO:0030057: desmosome

ECO:0000314: direct assay evidence used in manual assertion

C

  • part_of:(EMAPA:25765)

Seeded From UniProt

complete

MOUSE:CADH1

part_of

GO:0005911: cell-cell junction

ECO:0000314: direct assay evidence used in manual assertion

C

part_of:(EMAPA:25765)|part_of:(EMAPA:25765)

Seeded From UniProt

complete

MOUSE:PLAK

part_of

GO:0030057: desmosome

ECO:0000314: direct assay evidence used in manual assertion

C

part_of:(EMAPA:25765)

Seeded From UniProt

complete


See also

References

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